<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019c716d-a552-7cf3-add7-c92312d2a6dc,g:e1f325fd-9c27-4857-8c05-8b6b222d42d9-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="https://xbrl.org/2023/arcrole/summation-item" xlink:type="simple" xlink:href="https://www.xbrl.org/2023/calculation-1.1.xsd#summation-item"/>
  <link:roleRef roleURI="http://www.krystalbio.com/role/CondensedConsolidatedBalanceSheets" xlink:type="simple" xlink:href="krys-20260331.xsd#CondensedConsolidatedBalanceSheets"/>
  <link:calculationLink xlink:role="http://www.krystalbio.com/role/CondensedConsolidatedBalanceSheets" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_019c716d-a5ed-72a6-a2bd-b223871fc966" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019c716d-a5ed-7204-8c2a-1f02a14cb7cc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019c716d-a5ed-72a6-a2bd-b223871fc966" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019c716d-a5ed-7204-8c2a-1f02a14cb7cc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_019c716d-a5ed-7752-9926-b1b7bbe7f84e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019c716d-a5ed-72a6-a2bd-b223871fc966" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_019c716d-a5ed-7752-9926-b1b7bbe7f84e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_019c716d-a5ed-7068-b33a-52a0eeb456e8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019c716d-a5ed-72a6-a2bd-b223871fc966" xlink:to="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_019c716d-a5ed-7068-b33a-52a0eeb456e8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_019c716d-a5ed-7923-8fe4-40024c5d6972" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019c716d-a5ed-72a6-a2bd-b223871fc966" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_019c716d-a5ed-7923-8fe4-40024c5d6972" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNet_019c716d-a5ed-7505-8d01-7f41b2aaacc4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InventoryNet"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019c716d-a5ed-72a6-a2bd-b223871fc966" xlink:to="loc_us-gaap_InventoryNet_019c716d-a5ed-7505-8d01-7f41b2aaacc4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidTaxes_019c716d-a5ed-7011-a431-41dc6b8a46ab" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PrepaidTaxes"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019c716d-a5ed-72a6-a2bd-b223871fc966" xlink:to="loc_us-gaap_PrepaidTaxes_019c716d-a5ed-7011-a431-41dc6b8a46ab" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_019c716d-a5ed-71fe-826f-75dc0a66b65f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Assets"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_019c716d-a5ed-7d3b-8474-a78d52294978" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019c716d-a5ed-71fe-826f-75dc0a66b65f" xlink:to="loc_us-gaap_AssetsCurrent_019c716d-a5ed-7d3b-8474-a78d52294978" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_019c716d-a5ed-7f0d-a00f-dce600282123" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019c716d-a5ed-71fe-826f-75dc0a66b65f" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_019c716d-a5ed-7f0d-a00f-dce600282123" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermInvestments_019c716d-a5ed-79f5-9608-eb7727220e41" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongTermInvestments"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019c716d-a5ed-71fe-826f-75dc0a66b65f" xlink:to="loc_us-gaap_LongTermInvestments_019c716d-a5ed-79f5-9608-eb7727220e41" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAsset_019c716d-a5ed-76e9-a91d-87486341e158" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeaseRightOfUseAsset"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019c716d-a5ed-71fe-826f-75dc0a66b65f" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAsset_019c716d-a5ed-76e9-a91d-87486341e158" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent_019c716d-a5ed-7d21-84f5-8df19f5eb18b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019c716d-a5ed-71fe-826f-75dc0a66b65f" xlink:to="loc_us-gaap_OtherAssetsNoncurrent_019c716d-a5ed-7d21-84f5-8df19f5eb18b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxAssetsNet_019c716d-a5ed-7bb7-9dd8-c434698fd53a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DeferredIncomeTaxAssetsNet"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019c716d-a5ed-71fe-826f-75dc0a66b65f" xlink:to="loc_us-gaap_DeferredIncomeTaxAssetsNet_019c716d-a5ed-7bb7-9dd8-c434698fd53a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019c716d-a5ed-7ec0-8b44-78def4f6d2d0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockValue_019c716d-a5ed-78ea-a418-0390319aa9a4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019c716d-a5ed-7ec0-8b44-78def4f6d2d0" xlink:to="loc_us-gaap_CommonStockValue_019c716d-a5ed-78ea-a418-0390319aa9a4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapital_019c716d-a5ed-7e16-a5c9-ec217feeeec3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdditionalPaidInCapital"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019c716d-a5ed-7ec0-8b44-78def4f6d2d0" xlink:to="loc_us-gaap_AdditionalPaidInCapital_019c716d-a5ed-7e16-a5c9-ec217feeeec3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_019c716d-a5ed-7992-b833-d0d00c1435a3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019c716d-a5ed-7ec0-8b44-78def4f6d2d0" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_019c716d-a5ed-7992-b833-d0d00c1435a3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_019c716d-a5ed-7de5-ada7-46ee1f3e97e6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019c716d-a5ed-7ec0-8b44-78def4f6d2d0" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_019c716d-a5ed-7de5-ada7-46ee1f3e97e6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity_019c716d-a5ed-7c07-8c9f-055a94b145f0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_019c716d-a5ed-7725-915c-258c8a30c857" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Liabilities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_019c716d-a5ed-7c07-8c9f-055a94b145f0" xlink:to="loc_us-gaap_Liabilities_019c716d-a5ed-7725-915c-258c8a30c857" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommitmentsAndContingencies_019c716d-a5ed-7dd8-8d4b-44910c107e4b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommitmentsAndContingencies"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_019c716d-a5ed-7c07-8c9f-055a94b145f0" xlink:to="loc_us-gaap_CommitmentsAndContingencies_019c716d-a5ed-7dd8-8d4b-44910c107e4b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019c716d-a5ed-748d-99fe-2caf8b284256" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_019c716d-a5ed-7c07-8c9f-055a94b145f0" xlink:to="loc_us-gaap_StockholdersEquity_019c716d-a5ed-748d-99fe-2caf8b284256" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_019c716d-a5ed-7b81-8dce-23168c0a1f18" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableAndOtherAccruedLiabilitiesCurrent_019c716d-a5ed-77d6-83eb-600d40b367ba" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccountsPayableAndOtherAccruedLiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019c716d-a5ed-7b81-8dce-23168c0a1f18" xlink:to="loc_us-gaap_AccountsPayableAndOtherAccruedLiabilitiesCurrent_019c716d-a5ed-77d6-83eb-600d40b367ba" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_019c716d-a5ed-7edd-a776-e4dee17a9229" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019c716d-a5ed-7b81-8dce-23168c0a1f18" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_019c716d-a5ed-7edd-a776-e4dee17a9229" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_AccruedRebatesCurrent_019c716d-a5ed-7c9e-a6c6-6ffbd0980ae0" xlink:href="krys-20260331.xsd#krys_AccruedRebatesCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019c716d-a5ed-7b81-8dce-23168c0a1f18" xlink:to="loc_krys_AccruedRebatesCurrent_019c716d-a5ed-7c9e-a6c6-6ffbd0980ae0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableCurrent_019c716d-a5ed-7351-b0b5-165b315de499" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccountsPayableCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019c716d-a5ed-7b81-8dce-23168c0a1f18" xlink:to="loc_us-gaap_AccountsPayableCurrent_019c716d-a5ed-7351-b0b5-165b315de499" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_019c716d-a5ed-7965-bfb1-ae359487b32c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Liabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_019c716d-a5ed-746f-b1e1-fbec4f8ee2c5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019c716d-a5ed-7965-bfb1-ae359487b32c" xlink:to="loc_us-gaap_LiabilitiesCurrent_019c716d-a5ed-746f-b1e1-fbec4f8ee2c5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_019c716d-a5ed-7f8a-a44f-42a28acbc8a4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019c716d-a5ed-7965-bfb1-ae359487b32c" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_019c716d-a5ed-7f8a-a44f-42a28acbc8a4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_019c716d-a5ed-7160-bd18-282f470cddd8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019c716d-a5ed-7965-bfb1-ae359487b32c" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_019c716d-a5ed-7160-bd18-282f470cddd8" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.krystalbio.com/role/CondensedConsolidatedStatementsofOperationsandComprehensiveIncome" xlink:type="simple" xlink:href="krys-20260331.xsd#CondensedConsolidatedStatementsofOperationsandComprehensiveIncome"/>
  <link:calculationLink xlink:role="http://www.krystalbio.com/role/CondensedConsolidatedStatementsofOperationsandComprehensiveIncome" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019c716d-a5ed-70d2-93f5-18bda13fe42b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019c716d-a5ed-7519-901e-36c5c2d66ada" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_019c716d-a5ed-70d2-93f5-18bda13fe42b" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019c716d-a5ed-7519-901e-36c5c2d66ada" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_019c716d-a5ed-795c-b338-01dabb4d6dc9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_019c716d-a5ed-70d2-93f5-18bda13fe42b" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_019c716d-a5ed-795c-b338-01dabb4d6dc9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_019c716d-a5ed-777d-b3c2-b657f06c906b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019c716d-a5ed-788a-8d7f-872f88f30490" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_019c716d-a5ed-777d-b3c2-b657f06c906b" xlink:to="loc_us-gaap_NetIncomeLoss_019c716d-a5ed-788a-8d7f-872f88f30490" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_019c716d-a5ed-7640-b743-a1129d442779" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_019c716d-a5ed-777d-b3c2-b657f06c906b" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_019c716d-a5ed-7640-b743-a1129d442779" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent_019c716d-a5ed-7590-8780-85ad4ce8491a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_019c716d-a5ed-777d-b3c2-b657f06c906b" xlink:to="loc_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent_019c716d-a5ed-7590-8780-85ad4ce8491a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_019c716d-a5ed-758e-89fc-4ff25253c238" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019c716d-a5ed-73ec-8f9c-6320243685c7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_019c716d-a5ed-758e-89fc-4ff25253c238" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019c716d-a5ed-73ec-8f9c-6320243685c7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_019c716d-a5ed-7a80-882b-a28bbd09c4af" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingExpenses"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_019c716d-a5ed-758e-89fc-4ff25253c238" xlink:to="loc_us-gaap_OperatingExpenses_019c716d-a5ed-7a80-882b-a28bbd09c4af" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019c716d-a5ed-70a4-844a-3e11cf2291ed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_019c716d-a5ed-7be3-97b8-8030cde13f88" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019c716d-a5ed-70a4-844a-3e11cf2291ed" xlink:to="loc_us-gaap_OperatingIncomeLoss_019c716d-a5ed-7be3-97b8-8030cde13f88" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestIncomeExpenseNonoperatingNet_019c716d-a5ed-7ef5-89d5-ab703732a065" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InterestIncomeExpenseNonoperatingNet"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019c716d-a5ed-70a4-844a-3e11cf2291ed" xlink:to="loc_us-gaap_InterestIncomeExpenseNonoperatingNet_019c716d-a5ed-7ef5-89d5-ab703732a065" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_019c716d-a5ed-758a-8399-f1b8f51765c2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingExpenses"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_CostOfGoodsAndServicesSoldOperating_019c716d-a5ed-77d9-853d-4fd3dd24a70f" xlink:href="krys-20260331.xsd#krys_CostOfGoodsAndServicesSoldOperating"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingExpenses_019c716d-a5ed-758a-8399-f1b8f51765c2" xlink:to="loc_krys_CostOfGoodsAndServicesSoldOperating_019c716d-a5ed-77d9-853d-4fd3dd24a70f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_019c716d-a5ed-7986-942d-9565eba7392c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingExpenses_019c716d-a5ed-758a-8399-f1b8f51765c2" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_019c716d-a5ed-7986-942d-9565eba7392c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_019c716d-a5ed-74a9-b502-46ec9cdd3b59" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingExpenses_019c716d-a5ed-758a-8399-f1b8f51765c2" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_019c716d-a5ed-74a9-b502-46ec9cdd3b59" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.krystalbio.com/role/CondensedConsolidatedStatementsofCashFlows" xlink:type="simple" xlink:href="krys-20260331.xsd#CondensedConsolidatedStatementsofCashFlows"/>
  <link:calculationLink xlink:role="http://www.krystalbio.com/role/CondensedConsolidatedStatementsofCashFlows" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019c716d-a5ed-70b5-84b0-a92a010d90fa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019c716d-a5ed-7871-b9b5-f52e973d310e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019c716d-a5ed-70b5-84b0-a92a010d90fa" xlink:to="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019c716d-a5ed-7871-b9b5-f52e973d310e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019c716d-a5ed-7911-a99f-b40de3e3bfdc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019c716d-a5ed-70b5-84b0-a92a010d90fa" xlink:to="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019c716d-a5ed-7911-a99f-b40de3e3bfdc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_019c716d-a5ed-78d9-9732-e100b05a7534" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019c716d-a5ed-70b5-84b0-a92a010d90fa" xlink:to="loc_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_019c716d-a5ed-78d9-9732-e100b05a7534" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7775-8581-6317d4af7274" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019c716d-a5ed-70b5-84b0-a92a010d90fa" xlink:to="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7775-8581-6317d4af7274" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019c716d-a5ed-71ec-be63-d6fffb1ef395" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_019c716d-a5ed-716c-b109-3e6eeef1c88a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019c716d-a5ed-71ec-be63-d6fffb1ef395" xlink:to="loc_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment_019c716d-a5ed-716c-b109-3e6eeef1c88a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_019c716d-a5ed-7c7c-8611-2c40e9a8e157" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019c716d-a5ed-71ec-be63-d6fffb1ef395" xlink:to="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_019c716d-a5ed-7c7c-8611-2c40e9a8e157" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireInvestments_019c716d-a5ed-7f0d-bdfd-4f9069c042cc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsToAcquireInvestments"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019c716d-a5ed-71ec-be63-d6fffb1ef395" xlink:to="loc_us-gaap_PaymentsToAcquireInvestments_019c716d-a5ed-7f0d-bdfd-4f9069c042cc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleMaturityAndCollectionOfShorttermInvestments_019c716d-a5ed-7f18-b199-d5506155a59d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProceedsFromSaleMaturityAndCollectionOfShorttermInvestments"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019c716d-a5ed-71ec-be63-d6fffb1ef395" xlink:to="loc_us-gaap_ProceedsFromSaleMaturityAndCollectionOfShorttermInvestments_019c716d-a5ed-7f18-b199-d5506155a59d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019c716d-a5ed-771c-81c8-73a3487223d5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromStockOptionsExercised_019c716d-a5ed-773d-b71b-426585ef7d1c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProceedsFromStockOptionsExercised"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019c716d-a5ed-771c-81c8-73a3487223d5" xlink:to="loc_us-gaap_ProceedsFromStockOptionsExercised_019c716d-a5ed-773d-b71b-426585ef7d1c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_019c716d-a5ed-7051-9cee-f5b03fd8bf7f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019c716d-a5ed-771c-81c8-73a3487223d5" xlink:to="loc_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_019c716d-a5ed-7051-9cee-f5b03fd8bf7f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RealizedInvestmentGainsLosses_019c716d-a5ed-7257-b17b-b693e485d1c5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RealizedInvestmentGainsLosses"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_RealizedInvestmentGainsLosses_019c716d-a5ed-7257-b17b-b693e485d1c5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensation_019c716d-a5ed-7f2e-b6e4-92e813439aa6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensation"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_ShareBasedCompensation_019c716d-a5ed-7f2e-b6e4-92e813439aa6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019c716d-a5ed-739a-8744-f5686e4f3e45" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_NetIncomeLoss_019c716d-a5ed-739a-8744-f5686e4f3e45" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_IncreaseDecreaseInLeaseLiability_019c716d-a5ed-7cd4-b08d-47061db8e9b5" xlink:href="krys-20260331.xsd#krys_IncreaseDecreaseInLeaseLiability"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_krys_IncreaseDecreaseInLeaseLiability_019c716d-a5ed-7cd4-b08d-47061db8e9b5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_AccretionExpenseNet_019c716d-a5ed-78f4-a1b6-0ecd974b1e73" xlink:href="krys-20260331.xsd#krys_AccretionExpenseNet"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_krys_AccretionExpenseNet_019c716d-a5ed-78f4-a1b6-0ecd974b1e73" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_019c716d-a5ed-73c3-9682-cb50b5ecac15" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_019c716d-a5ed-73c3-9682-cb50b5ecac15" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherOperatingActivitiesCashFlowStatement_019c716d-a5ed-7247-9e72-93520358b296" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherOperatingActivitiesCashFlowStatement"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_OtherOperatingActivitiesCashFlowStatement_019c716d-a5ed-7247-9e72-93520358b296" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_IncreaseDecreaseInAccruedRebates_019c716d-a5ed-7689-a430-3195b233f9b2" xlink:href="krys-20260331.xsd#krys_IncreaseDecreaseInAccruedRebates"/>
    <link:calculationArc order="8" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_krys_IncreaseDecreaseInAccruedRebates_019c716d-a5ed-7689-a430-3195b233f9b2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsPayable_019c716d-a5ed-740f-8aff-348da2de5c72" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInAccountsPayable"/>
    <link:calculationArc order="9" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsPayable_019c716d-a5ed-740f-8aff-348da2de5c72" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInInventories_019c716d-a5ed-7761-bc84-674e258bddd0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInInventories"/>
    <link:calculationArc order="10" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_IncreaseDecreaseInInventories_019c716d-a5ed-7761-bc84-674e258bddd0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Depreciation_019c716d-a5ed-740e-a7d6-5e63d93ca78e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Depreciation"/>
    <link:calculationArc order="11" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_Depreciation_019c716d-a5ed-740e-a7d6-5e63d93ca78e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_019c716d-a5ed-79d7-8cec-25e1e688d818" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable"/>
    <link:calculationArc order="12" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_019c716d-a5ed-79d7-8cec-25e1e688d818" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_IncreaseDecreaseAccruedLegalSettlementAndInProcessResearchAndDevelopment_019c716d-a5ed-77a3-be90-c471b986a67a" xlink:href="krys-20260331.xsd#krys_IncreaseDecreaseAccruedLegalSettlementAndInProcessResearchAndDevelopment"/>
    <link:calculationArc order="13" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_krys_IncreaseDecreaseAccruedLegalSettlementAndInProcessResearchAndDevelopment_019c716d-a5ed-77a3-be90-c471b986a67a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccruedLiabilitiesAndOtherOperatingLiabilities_019c716d-a5ed-76be-93fb-04910429da56" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilitiesAndOtherOperatingLiabilities"/>
    <link:calculationArc order="14" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_IncreaseDecreaseInAccruedLiabilitiesAndOtherOperatingLiabilities_019c716d-a5ed-76be-93fb-04910429da56" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_019c716d-a5ed-7948-8174-a42c4b9c4890" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense"/>
    <link:calculationArc order="15" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_019c716d-a5ed-7948-8174-a42c4b9c4890" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInOtherNoncurrentLiabilities_019c716d-a5ed-7c25-9a30-61b5091adc2f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInOtherNoncurrentLiabilities"/>
    <link:calculationArc order="16" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_IncreaseDecreaseInOtherNoncurrentLiabilities_019c716d-a5ed-7c25-9a30-61b5091adc2f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInPrepaidTaxes_019c716d-a5ed-7a9f-bc3c-209bbc20637f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInPrepaidTaxes"/>
    <link:calculationArc order="17" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019c716d-a5ed-7b28-a61a-24c3c2d0222f" xlink:to="loc_us-gaap_IncreaseDecreaseInPrepaidTaxes_019c716d-a5ed-7a9f-bc3c-209bbc20637f" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.krystalbio.com/role/NetIncomePerShareAttributabletoCommonStockholdersScheduleofNetIncomeLossPerShareAttributabletoCommonStockholdersDetails" xlink:type="simple" xlink:href="krys-20260331.xsd#NetIncomePerShareAttributabletoCommonStockholdersScheduleofNetIncomeLossPerShareAttributabletoCommonStockholdersDetails"/>
  <link:calculationLink xlink:role="http://www.krystalbio.com/role/NetIncomePerShareAttributabletoCommonStockholdersScheduleofNetIncomeLossPerShareAttributabletoCommonStockholdersDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019de06b-d045-7b5e-9629-c7f8bc675718" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_019de06b-d045-70d5-9041-e6c64f42a9fa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019de06b-d045-7b5e-9629-c7f8bc675718" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_019de06b-d045-70d5-9041-e6c64f42a9fa" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_019de06b-d045-70cf-a2fb-1242a5618140" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019de06b-d045-7b5e-9629-c7f8bc675718" xlink:to="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_019de06b-d045-70cf-a2fb-1242a5618140" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.krystalbio.com/role/FairValueInstrumentsScheduleofCashCashEquivalentsandAvailableforSaleSecuritiesDetails" xlink:type="simple" xlink:href="krys-20260331.xsd#FairValueInstrumentsScheduleofCashCashEquivalentsandAvailableforSaleSecuritiesDetails"/>
  <link:calculationLink xlink:role="http://www.krystalbio.com/role/FairValueInstrumentsScheduleofCashCashEquivalentsandAvailableforSaleSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSaleAmortizedCost_019c716d-a69c-7114-9ecf-44a89bf2aae5" xlink:href="krys-20260331.xsd#krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSaleAmortizedCost"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019c716d-a69c-7c0a-9116-0cbddd610433" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSaleAmortizedCost_019c716d-a69c-7114-9ecf-44a89bf2aae5" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019c716d-a69c-7c0a-9116-0cbddd610433" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSale_019c716d-a69c-7042-907d-521985af681f" xlink:href="krys-20260331.xsd#krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSale"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSaleAmortizedCost_019c716d-a69c-7114-9ecf-44a89bf2aae5" xlink:to="loc_krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSale_019c716d-a69c-7042-907d-521985af681f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019c716d-a69c-7365-976e-85d390719c34" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSaleAmortizedCost_019c716d-a69c-7114-9ecf-44a89bf2aae5" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019c716d-a69c-7365-976e-85d390719c34" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSale_019c716d-a69c-79c7-af53-7d3c3b728d0d" xlink:href="krys-20260331.xsd#krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSale"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019c716d-a69c-71dc-821c-463ea189f1a3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSale_019c716d-a69c-79c7-af53-7d3c3b728d0d" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019c716d-a69c-71dc-821c-463ea189f1a3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019c716d-a69c-7258-951a-4c8777350a80" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSale_019c716d-a69c-79c7-af53-7d3c3b728d0d" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019c716d-a69c-7258-951a-4c8777350a80" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019c716d-a69c-7202-99a3-8c77dbcbb697" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019c716d-a69c-7501-9944-75f6cec28bfa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019c716d-a69c-7202-99a3-8c77dbcbb697" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019c716d-a69c-7501-9944-75f6cec28bfa" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019c716d-a69c-755c-aa0d-97db07eeb88d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019c716d-a69c-7202-99a3-8c77dbcbb697" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019c716d-a69c-755c-aa0d-97db07eeb88d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019c716d-a69c-7bc4-b1cb-d6a5bdb9b877" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019c716d-a69c-7202-99a3-8c77dbcbb697" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019c716d-a69c-7bc4-b1cb-d6a5bdb9b877" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.krystalbio.com/role/FairValueInstrumentsScheduleofCashCashEquivalentsandAvailableforSaleSecuritiesDetails_1" xlink:type="simple" xlink:href="krys-20260331.xsd#FairValueInstrumentsScheduleofCashCashEquivalentsandAvailableforSaleSecuritiesDetails_1"/>
  <link:calculationLink xlink:role="http://www.krystalbio.com/role/FairValueInstrumentsScheduleofCashCashEquivalentsandAvailableforSaleSecuritiesDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSaleAmortizedCost_019c716d-a69c-73f7-a7d0-11cbbf8a942b" xlink:href="krys-20260331.xsd#krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSaleAmortizedCost"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019c716d-a69c-7a41-ba45-95111edf1f9f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSaleAmortizedCost_019c716d-a69c-73f7-a7d0-11cbbf8a942b" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019c716d-a69c-7a41-ba45-95111edf1f9f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019c716d-a69c-7934-b90e-4280b71c893f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSaleAmortizedCost_019c716d-a69c-73f7-a7d0-11cbbf8a942b" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019c716d-a69c-7934-b90e-4280b71c893f" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.krystalbio.com/role/BalanceSheetComponentsScheduleofInventoryDetails" xlink:type="simple" xlink:href="krys-20260331.xsd#BalanceSheetComponentsScheduleofInventoryDetails"/>
  <link:calculationLink xlink:role="http://www.krystalbio.com/role/BalanceSheetComponentsScheduleofInventoryDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNet_019c716d-a69c-7828-a887-351c43855575" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InventoryNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryFinishedGoodsNetOfReserves_019c716d-a69c-75f1-9aa2-7ef8c54ef37c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InventoryFinishedGoodsNetOfReserves"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_019c716d-a69c-7828-a887-351c43855575" xlink:to="loc_us-gaap_InventoryFinishedGoodsNetOfReserves_019c716d-a69c-75f1-9aa2-7ef8c54ef37c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryRawMaterialsNetOfReserves_019c716d-a69c-78a2-a983-0834e4526067" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InventoryRawMaterialsNetOfReserves"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_019c716d-a69c-7828-a887-351c43855575" xlink:to="loc_us-gaap_InventoryRawMaterialsNetOfReserves_019c716d-a69c-78a2-a983-0834e4526067" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryWorkInProcessNetOfReserves_019c716d-a69c-7fc9-af94-6384cada2a3a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InventoryWorkInProcessNetOfReserves"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_019c716d-a69c-7828-a887-351c43855575" xlink:to="loc_us-gaap_InventoryWorkInProcessNetOfReserves_019c716d-a69c-7fc9-af94-6384cada2a3a" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.krystalbio.com/role/BalanceSheetComponentsScheduleofPropertyandEquipmentNetDetail" xlink:type="simple" xlink:href="krys-20260331.xsd#BalanceSheetComponentsScheduleofPropertyandEquipmentNetDetail"/>
  <link:calculationLink xlink:role="http://www.krystalbio.com/role/BalanceSheetComponentsScheduleofPropertyandEquipmentNetDetail" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_019c716d-a69c-7d95-9f3b-04f2695a08f4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_019c716d-a69c-71c3-b822-d01a853b8ba4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNet_019c716d-a69c-7d95-9f3b-04f2695a08f4" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_019c716d-a69c-71c3-b822-d01a853b8ba4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_019c716d-a69c-75d4-8487-d43017a041d4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNet_019c716d-a69c-7d95-9f3b-04f2695a08f4" xlink:to="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_019c716d-a69c-75d4-8487-d43017a041d4" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.krystalbio.com/role/BalanceSheetComponentsScheduleofAccruedExpensesAndOtherCurrentLiabilitiesDetails" xlink:type="simple" xlink:href="krys-20260331.xsd#BalanceSheetComponentsScheduleofAccruedExpensesAndOtherCurrentLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.krystalbio.com/role/BalanceSheetComponentsScheduleofAccruedExpensesAndOtherCurrentLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_krys_AccruedExpensesAndOtherCurrentLiabilities_019c716d-a69c-72e0-a85d-ae2fe33cbb4a" xlink:href="krys-20260331.xsd#krys_AccruedExpensesAndOtherCurrentLiabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_AccruedInventory_019c716d-a69c-7174-a4ee-deb2354638ea" xlink:href="krys-20260331.xsd#krys_AccruedInventory"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_AccruedExpensesAndOtherCurrentLiabilities_019c716d-a69c-72e0-a85d-ae2fe33cbb4a" xlink:to="loc_krys_AccruedInventory_019c716d-a69c-7174-a4ee-deb2354638ea" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedIncomeTaxes_019c716d-a69c-7c46-85ec-d7a3930c8383" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccruedIncomeTaxes"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_AccruedExpensesAndOtherCurrentLiabilities_019c716d-a69c-72e0-a85d-ae2fe33cbb4a" xlink:to="loc_us-gaap_AccruedIncomeTaxes_019c716d-a69c-7c46-85ec-d7a3930c8383" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_AccruedPreclinicalAndClinicalExpenses_019c716d-a69c-78cc-837f-6c3a667c5f6b" xlink:href="krys-20260331.xsd#krys_AccruedPreclinicalAndClinicalExpenses"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_AccruedExpensesAndOtherCurrentLiabilities_019c716d-a69c-72e0-a85d-ae2fe33cbb4a" xlink:to="loc_krys_AccruedPreclinicalAndClinicalExpenses_019c716d-a69c-78cc-837f-6c3a667c5f6b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_AccruedPayrollAndBenefits_019c716d-a69c-7ed6-b887-3995789ceb28" xlink:href="krys-20260331.xsd#krys_AccruedPayrollAndBenefits"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_AccruedExpensesAndOtherCurrentLiabilities_019c716d-a69c-72e0-a85d-ae2fe33cbb4a" xlink:to="loc_krys_AccruedPayrollAndBenefits_019c716d-a69c-7ed6-b887-3995789ceb28" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedProfessionalFeesCurrent_019c716d-a69c-7b1a-b18a-999b67c925e9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccruedProfessionalFeesCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_AccruedExpensesAndOtherCurrentLiabilities_019c716d-a69c-72e0-a85d-ae2fe33cbb4a" xlink:to="loc_us-gaap_AccruedProfessionalFeesCurrent_019c716d-a69c-7b1a-b18a-999b67c925e9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_AccruedConstructionInProgressCurrent_019c716d-a69c-7d85-8bee-ce0a03d2606e" xlink:href="krys-20260331.xsd#krys_AccruedConstructionInProgressCurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_AccruedExpensesAndOtherCurrentLiabilities_019c716d-a69c-72e0-a85d-ae2fe33cbb4a" xlink:to="loc_krys_AccruedConstructionInProgressCurrent_019c716d-a69c-7d85-8bee-ce0a03d2606e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesCurrent_019c716d-a69c-77a3-ba3e-c4fb004081bf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherLiabilitiesCurrent"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_krys_AccruedExpensesAndOtherCurrentLiabilities_019c716d-a69c-72e0-a85d-ae2fe33cbb4a" xlink:to="loc_us-gaap_OtherLiabilitiesCurrent_019c716d-a69c-77a3-ba3e-c4fb004081bf" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.krystalbio.com/role/LeasesScheduleofFutureMinimumOperatingLeasePaymentsDetails" xlink:type="simple" xlink:href="krys-20260331.xsd#LeasesScheduleofFutureMinimumOperatingLeasePaymentsDetails"/>
  <link:calculationLink xlink:role="http://www.krystalbio.com/role/LeasesScheduleofFutureMinimumOperatingLeasePaymentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019c716d-a69c-7819-8e7b-d38899c62475" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_019c716d-a69c-799d-8986-65b8dbcb1276" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019c716d-a69c-7819-8e7b-d38899c62475" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_019c716d-a69c-799d-8986-65b8dbcb1276" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiability_019c716d-a69c-79dd-9ac0-2501ab0989ec" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeaseLiability"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019c716d-a69c-7819-8e7b-d38899c62475" xlink:to="loc_us-gaap_OperatingLeaseLiability_019c716d-a69c-79dd-9ac0-2501ab0989ec" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.krystalbio.com/role/LeasesScheduleofFutureMinimumOperatingLeasePaymentsDetails_1" xlink:type="simple" xlink:href="krys-20260331.xsd#LeasesScheduleofFutureMinimumOperatingLeasePaymentsDetails_1"/>
  <link:calculationLink xlink:role="http://www.krystalbio.com/role/LeasesScheduleofFutureMinimumOperatingLeasePaymentsDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019c716d-a69c-73b6-b1b4-51b9588320a1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear_019c716d-a69c-7646-9a57-b8d6b504343b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019c716d-a69c-73b6-b1b4-51b9588320a1" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear_019c716d-a69c-7646-9a57-b8d6b504343b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_019c716d-a69c-7f89-bb91-6dd89dde3e48" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019c716d-a69c-73b6-b1b4-51b9588320a1" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_019c716d-a69c-7f89-bb91-6dd89dde3e48" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_krys_LesseeOperatingLeaseLiabilityToBePaidAfterYearFour_019c716d-a69c-780a-a069-e5a1914e1343" xlink:href="krys-20260331.xsd#krys_LesseeOperatingLeaseLiabilityToBePaidAfterYearFour"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019c716d-a69c-73b6-b1b4-51b9588320a1" xlink:to="loc_krys_LesseeOperatingLeaseLiabilityToBePaidAfterYearFour_019c716d-a69c-780a-a069-e5a1914e1343" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_019c716d-a69c-7b16-b8a4-d2e57571ccb9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019c716d-a69c-73b6-b1b4-51b9588320a1" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_019c716d-a69c-7b16-b8a4-d2e57571ccb9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_019c716d-a69c-7d64-b079-bbf1b43c6513" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019c716d-a69c-73b6-b1b4-51b9588320a1" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_019c716d-a69c-7d64-b079-bbf1b43c6513" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_019c716d-a69c-7281-aa62-f0056c6f6b90" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019c716d-a69c-73b6-b1b4-51b9588320a1" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_019c716d-a69c-7281-aa62-f0056c6f6b90" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.krystalbio.com/role/LeasesScheduleofLeaseExpenseDetails" xlink:type="simple" xlink:href="krys-20260331.xsd#LeasesScheduleofLeaseExpenseDetails"/>
  <link:calculationLink xlink:role="http://www.krystalbio.com/role/LeasesScheduleofLeaseExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseCost_019c716d-a69c-7d07-84bf-aa9737ac0e8d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LeaseCost"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseCost_019c716d-a69c-7aff-9199-7dea210d6978" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeaseCost"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LeaseCost_019c716d-a69c-7d07-84bf-aa9737ac0e8d" xlink:to="loc_us-gaap_OperatingLeaseCost_019c716d-a69c-7aff-9199-7dea210d6978" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableLeaseCost_019c716d-a69c-7566-a849-28a5f812a8b5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VariableLeaseCost"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LeaseCost_019c716d-a69c-7d07-84bf-aa9737ac0e8d" xlink:to="loc_us-gaap_VariableLeaseCost_019c716d-a69c-7566-a849-28a5f812a8b5" xlink:type="arc"/>
  </link:calculationLink>
</link:linkbase>
