−Removed: We are a fully integrated, commercial-stage biotechnology company focused on the discovery, development, manufacturing and commercialization of genetic medicines to treat diseases with high unmet medical needs.
+Added: We are a fully integrated, global, commercial-stage biotechnology company focused on the discovery, development, manufacturing and commercialization of genetic medicines to treat diseases with high unmet medical needs.
Using our patented gene therapy technology platform that is based on engineered herpes simplex virus-1 (“HSV-1”), we create vectors that efficiently deliver therapeutic transgenes to cells of interest in multiple organ systems.
The cell’s own machinery then transcribes and translates the transgene to treat the disease.
−Removed: Our vectors are amenable to formulation for non-invasive or minimally invasive routes of administration at a healthcare professional’s office or in the patient’s home by a healthcare professional.
+Added: Our vectors are amenable to formulation for non-invasive or minimally invasive routes of administration at a healthcare professional’s office or in the patient’s home by a healthcare professional, caregiver, or directly by the patient themselves.
Our innovative technology platform is supported by two in-house, commercial scale Current Good Manufacturing Practice (“CGMP”) manufacturing facilities.
−Removed: Our development pipeline includes multiple clinical stage programs for rare and serious diseases, and we are investing in research and development to advance and grow this pipeline.
−Removed: We possess exclusive rights to develop, manufacture, and commercialize our FDA approved product and our pipeline candidates throughout the world.
−Removed: While our focus is on the development of gene therapies to treat patients with severe, life‑threatening, or rare diseases with high unmet medical needs, we are also evaluating the potential of our platform to address more prevalent and/or non-genetic conditions.
−Removed: To that end, in April 2019, we incorporated Jeune Aesthetics, Inc.
−Removed: (“Jeune Aesthetics”), a wholly-owned subsidiary, for the purposes of undertaking preclinical and clinical studies for aesthetic skin conditions.
+Added: Our first commercial product, VYJUVEK ® , is now approved in the United States, the European Union (“EU”), and Japan for the treatment of dystrophic epidermolysis bullosa (“DEB”).
+Added: We launched VYJUVEK in the United States in 2023 and started launching VYJUVEK in Europe and Japan in 2025.
+Added: Our development pipeline includes multiple clinical stage product candidates for the treatment of rare and serious diseases, and we are investing in research and development to advance and grow this pipeline.
+Added: We possess exclusive rights to develop, manufacture, and commercialize VYJUVEK and our pipeline product candidates throughout the world.
+Added: While our focus is on the development of gene therapies to treat patients with rare diseases with high unmet medical needs, we are also evaluating the potential of our platform to address more common severe or life-threatening diseases, such as non-small cell lung cancer (“NSCLC”), as well as aesthetic conditions via our wholly-owned subsidiary Jeune Aesthetics, Inc.
+Added: (“Jeune Aesthetics”), which we incorporated in April 2019.
Our Redosable Gene Therapy Platform
22 unchanged sentences
Poor transduction efficiency has remained a major hurdle for direct delivery of most vectors particularly in the epithelia of the skin and lung.
−Removed: HSV-1 has a natural affinity, or tropism, for epithelial cells.
+Added: HSV-1 has a natural affinity, or tropism, for
+Added: epithelial cells.
Consequently, we believe our vector penetrates and delivers its payload much more efficiently than other vectors, resulting in transduction efficiencies or cell penetration as high as 95% in cell-based studies.
−Removed: The greater payload capacity of our vector and the high transduction efficiencies achieved allow us to deliver a
−Removed: full gene (or genes) directly to any patient’s tissues for off-the-shelf, in vivo gene expression without additional manipulation.
+Added: The greater payload capacity of our vector and the high transduction efficiencies achieved allow us to deliver a full gene (or genes) directly to any patient’s tissues for off-the-shelf, in vivo gene expression without additional manipulation.
• Direct Delivery :
12 unchanged sentences
Our scientific team’s collective decades of experience and expertise in HSV engineering and purification has allowed us to successfully optimize our engineered HSV-1 vector production process and develop in-house Chemistry, Manufacturing, and Controls (“CMC”) capabilities.
−Removed: • First Approval for Platform Builds on Existing Regulatory Precedent :
−Removed: The first FDA and European Medicines Agency (“EMA”)-approved oncolytic virus product, Imlygic ® by Amgen, for treatment of melanoma, a skin cancer, is based on a genetically engineered HSV-1 virus.
−Removed: Because this product also employs an HSV-1 backbone for chronic administration, it created a regulatory precedent for approval of an HSV-1-based chronic gene therapy.
−Removed: Now, with the FDA approval our first platform product, VYJUVEK, regulatory precedent for our proprietary HSV-1-based platform has also been established, and regulator familiarity with HSV-1 and our platform continues to grow.
+Added: • Regulatory Precedent and Platform Recognition :
+Added: With the approval of our first platform product, VYJUVEK, in the United States, EU, and Japan, regulatory precedent for our proprietary HSV-1-based platform has been established, and regulator familiarity with HSV-1 and our platform continues to grow.
+Added: Reflecting this increasing familiarity, in October 2025, the FDA granted platform technology designation to our genetically modified, non-replicating HSV-1 viral vector used in our product candidate, KB801 for the treatment of neurotrophic keratitis.
+Added: The FDA’s platform technology designation program is intended to provide efficiencies in drug development, manufacturing, and review processes for drug product applications that incorporate designated platform technologies.
+Added: The designation recognizes the reproducibility and scalability of our platform and its potential to support the development of multiple biologic products without compromising quality, manufacturing, or safety.
The above listed benefits of our innovative platform, and compatibility with formulation for topical, injectable, and inhaled delivery, make it the ideal choice to treat diseases and conditions of the skin, lung, and eye.
−Removed: Our FDA Approved Product and Pipeline
−Removed: The following table summarizes information regarding our FDA approved product, VYJUVEK, and product candidates in various stages of clinical and preclinical development as of the date of this Annual Report:
−Removed: Our FDA Approved Commercial Product
+Added: Our Commercial Product and Pipeline
+Added: The following table summarizes information regarding our commercial product, VYJUVEK, and product candidates in various stages of clinical and preclinical development as of the date of this Annual Report:
+Added: Our Commercial Product
VYJUVEK (beremagene geperpavec-svdt, or B-VEC;
−Removed: referred to as B-VEC outside the United States)
+Added: referred to as B-VEC outside the United States, Europe, and Japan)
Disease Background
7 unchanged sentences
Prior to the approval of VYJUVEK, the standard of care for DEB patients had been limited to palliative measures that seek to provide relief from some of the symptoms of DEB but do not meaningfully impact disease outcomes.
−Removed: B-VEC is a redosable, off-the-shelf gene therapy designed to deliver two copies of the COL7A1 gene when applied topically, directly onto an open wound.
−Removed: Unlike the previous standard of care, B-VEC treats DEB at the molecular level by providing the patient’s skin cells the template to make normal COL7 protein, thereby addressing the fundamental disease-causing mechanism.
−Removed: B-VEC was specifically designed to be easily administered by a healthcare professional in a doctor’s office or at the patient’s home.
−Removed: B-VEC was approved by the FDA in May 2023 and is marketed as VYJUVEK in the United States.
−Removed: We believe our approach to treating DEB is positively differentiated relative to palliative approaches, which do not address the underlying genetic cause of DEB or impact the durability of wound closure, and other known efforts to develop corrective treatments that employ autologous approaches.
+Added: VYJUVEK is a redosable, off-the-shelf gene therapy designed to deliver two copies of the COL7A1 gene when applied topically, directly onto an open wound.
+Added: Unlike the previous standard of care, VYJUVEK treats DEB at the molecular level by providing the patient’s skin cells the template to make normal COL7 protein, thereby addressing the fundamental disease-causing mechanism.
+Added: VYJUVEK was specifically designed to be easily administered in a doctor’s office or at the patient’s home.
+Added: VYJUVEK was first approved by FDA in 2023 for sale in the United States and, in 2025, was approved by European and Japanese regulators for sale in the EU and Japan.
+Added: We believe our approach to treating DEB is positively differentiated relative to palliative approaches, which do not address the underlying genetic cause of DEB or impact the durability of wound closure, and corrective treatments that employ autologous approaches.
Autologous treatments use a patient’s own tissues and cells to manufacture an individualized therapy.
−Removed: Such therapies tend to be expensive, invasive and time consuming to use, and require extensive patient travel, extended hospital stays, highly sophisticated medical teams and procedures.
−Removed: Commercial Launch
−Removed: We launched VYJUVEK, the first FDA approved treatment for DEB and the first and only corrective therapy for DEB, in the United States in August 2023.
+Added: Such therapies tend to be expensive, invasive and time consuming to use, and require extensive patient travel, extended hospital stays, and highly sophisticated medical teams and procedures.
+Added: Commercial Launches
+Added: We possess exclusive rights to commercialize VYJUVEK throughout the world.
+Added: We are commercializing VYJUVEK directly in the United States, major European markets, and Japan.
+Added: We first launched VYJUVEK in the United States in 2023.
We estimate that there are over 3,000 patients in the United States suffering from DEB, of which 1,200 were identified at launch through claims analytics and pre-launch patient identification activities conducted by our commercial field force.
−Removed: Since our commercial launch of VYJUVEK in the United States, we have reported $341.2 million in net product revenue.
−Removed: Our market access team has successfully secured strong nationwide coverage across the United States including, as of February 2025, positive policies or coverage decisions from plans covering over 97% of commercial and Medicaid lives.
−Removed: In January 2024, we announced that the United States Centers for Medicare & Medicaid Services (“CMS”) had assigned a permanent and product-specific J-code for VYJUVEK, effective on January 1, 2024.
−Removed: Preparations and infrastructure build out are underway in Europe and Japan to support direct commercial launch by Krystal in these regions, which is expected in 2025.
−Removed: Outside of the United States, major European markets and Japan, we intend to and have started entering into distribution arrangements with specialty distributors to commercialize VYJUVEK.
−Removed: We sell VYJUVEK to a limited number of specialty pharmacy (“SPs”) providers that mix the medication to be administered by a healthcare professional in either a healthcare professional or home setting and to a limited number of hospitals or specialty distributors (“SDs”) who deliver to hospitals where patients are administered the medication in a healthcare setting.
+Added: In August 2025, we launched VYJUVEK in Germany, our first commercial launch outside the United States, and in October 2025, we launched VYJUVEK in France under the post-marketing authorization early reimbursed access Accès Précoce program.
+Added: Over 1,000 DEB patients are already identified across both of these countries.
+Added: Pricing negotiations are underway in both Germany and France and are expected to continue until at least the second half of 2026 in Germany and until 2027 in France.
+Added: We are advancing pricing discussions with Italian reimbursement authorities to enable a potential launch in Italy in the second half of 2026.
+Added: We are initiating pricing discussions with relevant authorities in other key Western European markets.
+Added: The timing of additional European launches is uncertain and will depend on the cadence and outcomes of regulatory interaction and pricing negotiations.
+Added: In October 2025, we launched VYJUVEK in Japan following successful completion of pricing negotiations with Japan’s Ministry of Health, Labour and Welfare (“MHLW”).
+Added: We contract with specialty distributors to commercialize VYJUVEK in territories outside of the United States, major European markets, and Japan.
+Added: To date, we have entered into distribution agreements with leading regional specialty distributors covering key markets in Central and Eastern Europe, the Middle East, and Turkey, with Israel representing our most recent addition in February 2026, and we expect to further expand our specialty distributor network during 2026.
+Added: Since our first commercial launch of VYJUVEK in the United States, we have reported $730.3 million in net product revenue.
Regulatory Status
3 unchanged sentences
We sold the PRV in the third quarter of 2023 for $100 million.
−Removed: The FDA had previously granted Orphan Drug Designation (“ODD”), Fast Track Designation, Rare Pediatric Designation (“RPDD”), and Regenerative Medicine Advanced Therapy to B-VEC for the treatment of DEB.
−Removed: In September 2023, we received a positive opinion from the EMA Pediatric Committee on the Pediatric Investigation Plan for B-VEC for the treatment of DEB.
−Removed: Based on this positive opinion, we expect to be eligible for up to an additional two years of marketing exclusivity in the EU, on top of the ten-year EU market exclusivity after market approval in the EU.
−Removed: The European regulatory authorities have also granted B-VEC Orphan Designation and PRIority MEdicines eligibility for B-VEC to treat DEB.
−Removed: In October 2023, we submitted a marketing authorization application (“MAA”) to the EMA for B-VEC for the treatment of DEB in patients from birth.
−Removed: In November 2023, we were notified that the MAA had been validated and was now under Committee for Medicinal Products for Human Use (“CHMP”) review.
−Removed: In February 2024, the EMA completed inspection of our manufacturing facility as part of the MAA review process and, in May 2024, European Union good manufacturing practice (“EU GMP”) certification was granted by the EMA.
−Removed: Based on recent interactions with the EMA, we expect a CHMP opinion on the MAA in the first quarter of 2025.
−Removed: In December 2023, B-VEC was granted ODD status for the treatment of DEB by the Japan Ministry of Health, Labour and Welfare, a designation which confers specific benefits for orphan drug development including priority review of applications, extended registration validity, and reduced development costs.
−Removed: In October 2024, we filed a Japan New Drug Application (“JNDA”) with Japan’s Pharmaceuticals and Medical Devices Agency (“PMDA”).
−Removed: The JNDA includes the results from an open label extension (“OLE”) study of B-VEC in Japanese patients (the “Japan OLE”), the design of which had been approved by the PMDA in July 2023.
−Removed: A decision on the JNDA by the PMDA is expected in the second half of 2025.
+Added: In September 2025, the FDA approved a label update for VYJUVEK that expanded the treatment eligible population to include DEB patients from birth and provided patients with greater dosing flexibility, including the option for VYJUVEK to be applied by a healthcare professional (“HCP”), caregiver, or directly by the patient themselves, either at home or in a healthcare setting.
+Added: The FDA previously granted Orphan Drug Designation (“ODD”), Fast Track Designation (“FTD”), Rare Pediatric Disease Designation (“RPDD”), and Regenerative Medicine Advanced Therapy (“RMAT”) to B-VEC for the treatment of DEB.
+Added: On April 23, 2025, the European Commission (the “EC”) granted marketing authorization to VYJUVEK for the treatment of wounds in patients with DEB starting from birth.
+Added: VYJUVEK is the first corrective medicine approved in the EU for the treatment of DEB.
+Added: The approval granted by the EC allows for flexible VYJUVEK dosing either at home or in healthcare setting, with the option for patient or caregiver administration if deemed appropriate by a HCP.
+Added: The EC decision authorizes the marketing of VYJUVEK in all EU member states, as well as Iceland, Norway and Liechtenstein.
+Added: Previously, in September 2023, we received a positive opinion from the European Medicines Agency (“EMA”) Pediatric Committee on the Pediatric Investigation Plan for B-VEC for the treatment of DEB.
+Added: Based on this positive opinion, we expect to be eligible for up to an additional two years of marketing exclusivity in the EU, on top of the ten-year EU market exclusivity granted upon marketing authorization in the EU.
+Added: European regulatory authorities also previously granted Orphan Designation and PRIority MEdicines eligibility to B-VEC for the treatment of DEB.
+Added: On July 24, 2025, Japan’s MHLW granted marketing authorization to VYJUVEK for the treatment of wounds in patients with DEB, starting from birth.
+Added: VYJUVEK is the first genetic medicine approved in Japan for the treatment of DEB.
+Added: The Japanese approval allows for dosing at home or in a healthcare setting, with the option for administration by patients or their family members.
+Added: Genetic testing is not a requirement for treatment.
+Added: The re-examination period for VYJUVEK in Japan is ten years.
+Added: Japanese regulatory authorities previously granted ODD status to B-VEC for the treatment of DEB, a designation which confers multiple benefits including extended registration validity.
+Added: Regulatory filings for the marketing authorization of B-VEC in additional global markets are planned or underway.
Clinical Development
13 unchanged sentences
We announced positive results from the GEM-3 trial in November 2021 and, in December 2022, full results from the GEM-3 trial were published in the New England Journal of Medicine.
−Removed: Following completion of the GEM-3 trial, we initiated an OLE to provide extension of B-VEC treatment for participants who completed the GEM-3 trial (“rollover participants”) and B-VEC treatment for newly enrolling participants (“naïve participants”) with DEB.
+Added: Following completion of the GEM-3 trial, we initiated an open label extension (“OLE”) study to provide extension of B-VEC treatment for participants who completed the GEM-3 trial (“rollover participants”) and B-VEC treatment for newly
+Added: enrolling participants (“naïve participants”) with DEB.
The OLE was a multi-center, open-label study of B-VEC for the topical treatment of DEB wounds.
−Removed: The study enrolled 47 participants in total, comprising of 24 rollover participants and 23 naïve participants, at five sites in the United States.
−Removed: In April 2022, following feedback from the FDA, we announced that patients enrolled in the OLE study would have the option to be dosed in their homes by a health care professional.
+Added: The study enrolled 47 participants in total, comprising 24 rollover participants and 23 naïve participants, at five sites in the United States.
+Added: In April 2022, following feedback from the FDA, we announced that patients enrolled in the OLE study would have the option to be dosed in their homes by a HCP.
The primary study objective was the assessment of safety and tolerability of extended dosing with B-VEC in a broader patient population.
1 unchanged sentence
The OLE study was concluded in the third quarter of 2023, and the safety profile continued to support the overall benefit-risk of B-VEC, with no new safety concerns noted with extended duration of dosing of B-VEC.
−Removed: We expect to disclose additional detailed study data at upcoming scientific meetings or in scientific publications.
−Removed: In July 2023, the PMDA in Japan officially accepted our OLE study of B-VEC in Japanese patients.
+Added: Full OLE study results were published in the American Journal of Clinical Dermatology in April 2025.
+Added: In July 2023, Japan’s Pharmaceuticals and Medical Devices Agency (“ PMDA”) officially accepted our OLE study of B-VEC in Japanese patients (the “Japan OLE”).
Following that acceptance, we initiated the Japan OLE study and completed study enrollment.
−Removed: In April 2024, the efficacy portion of the Japan OLE study was completed with results that closely mirrored those of our Phase 3 GEM-3 trial in the United States.
+Added: In April 2024, the efficacy portion of the Japan OLE study was completed with results that closely mirrored those of our GEM-3 trial in the United States.
B-VEC was well tolerated in the Japanese study population, with a safety profile consistent with previous studies, and all four patients that completed the study achieved the primary endpoint of complete wound closure at six months.
−Removed: Details of the study can be found at jrct.niph.go.jp under JRCT ID jRCT2053230075.
−Removed: Our Pipeline Programs
−Removed: Ophthalmology
−Removed: KB803 (Ophthalmic B-VEC) for Ocular Complications of DEB
−Removed: Disease Background
−Removed: DEB is a rare and severe monogenic blistering disease that affects not only the skin, but also mucosal tissues dependent on COL7 anchoring fibrils for maintaining epithelial lining integrity.
−Removed: This includes the eye, where COL7 anchors the corneal epithelium.
−Removed: For a meaningful proportion of DEB patients, the genetic defect in COL7A1 results in loss or malfunctioning of these anchoring fibrils causing ocular complications, such as corneal erosions, abrasions, blistering, and scarring, that can lead to progressive vision loss.
−Removed: Over 50% of patients with recessive form of DEB and an estimated 10% of patients with the dominant form of DEB are thought to suffer from ocular complications.
−Removed: Correspondingly, we believe there are over 750 patients in the United States and over 2,000 worldwide that are affected.
−Removed: Disease management varies from supportive care and wound management to surgical interventions to remove scar tissue.
−Removed: No corrective or FDA approved therapies are presently available.
−Removed: KB803 (Ophthalmic B-VEC)
−Removed: KB803 is a redosable eye drop formulation of B-VEC, designed to deliver two copies of the COL7A1 transgene to the epithelial cells in a patient’s eye to produce COL7 protein.
−Removed: As with VYJUVEK, the goal of therapy with KB803 is to treat the disease locally, at the molecular level, by providing the patient’s epithelial cells of the eye the template to make normal COL7 protein, and thereby address the fundamental disease-causing mechanism.
−Removed: In preclinical studies, single and repeated topical B-VEC administration to the eye in a mouse corneal lesion model resulted in localized COL7A1 expression with no adverse effects noted histologically.
−Removed: B-VEC has been applied topically to the eye of one DEB patient under a compassionate use protocol.
−Removed: The clinical observations of this compassionate use case were published in the New England Journal of Medicine in February 2024.
−Removed: The patient presented with severe cicatrizing conjunctivitis secondary to DEB.
−Removed: Surgical symblepharon lysis of the patient’s right eye with pannus removal was conducted and regular administration of B-VEC as an eye drop directly to the eye (5×10 9 PFU/mL) were added to routine post-surgical care, three times weekly for the first two weeks and then once weekly.
−Removed: B-VEC application frequency was further decreased to once monthly once the corneal epithelium was healed.
−Removed: B-VEC was well tolerated with no drug-related adverse events noted.
−Removed: Full corneal healing was observed at three months, as well as significant visual acuity improvement from hand motion to 20/25 by eight months.
−Removed: In February 2024, the FDA agreed with our proposed single arm, open label registrational Phase 3 study design to enable approval of KB803 to treat ocular complications secondary to DEB.
−Removed: We expect to initiate the study in the first half of 2025 and plan to enroll up to 30 DEB patients.
−Removed: In August 2024, we initiated a natural history study to prospectively collect data on the frequency of corneal abrasions in patients with DEB and serve as a run-in period for patients who may be eligible to participate in the registrational Phase 3 study.
−Removed: We have enrolled approximately 50 DEB patients in the natural history study to date.
−Removed: Enrollment in the study is ongoing.
−Removed: Details of the natural history study can be found at www.clinicaltrials.gov under NCT identifier NCT06563414.
+Added: Results of the Japan OLE study were published the Journal of Dermatology in July 2025.
KB407 for Cystic Fibrosis (“CF”)
10 unchanged sentences
By enabling expression of full-length, normal CFTR protein in the lung, treatment with KB407 has potential to restore ion and water flow into and out of lung cells to correct the lung manifestations of the disease in patients regardless of their underlying genetic mutation.
−Removed: Preclinical efforts to date have shown that KB407 successfully transduces patient-derived epithelial cells and delivers functional CFTR in vitro in 2D and 3D organotypic systems, and is amendable to non-invasive inhaled administration in vivo , as indicated by successful delivery to the lungs through the use of a clinically relevant nebulizer in small animal models.
+Added: Preclinical efforts show that KB407 successfully transduces patient-derived epithelial cells and delivers functional CFTR in vitro in 2D and 3D organotypic systems, and is amendable to non-invasive inhaled administration in vivo , as indicated by successful delivery to the lungs through the use of a clinically relevant nebulizer in small animal models.
Successful delivery and distribution throughout the lung also was observed in nonhuman primates.
4 unchanged sentences
In December 2024, we announced an interim safety data update for patients treated with KB407 in the first two dose escalation cohorts.
−Removed: Both single and repeat inhaled administration of KB407 were well tolerated with only mild to moderate and transient adverse events observed.
−Removed: We expect to report safety and CFTR delivery data from patients in the third and final cohort in the middle of 2025.
−Removed: Details of the CORAL-1 study can be found at www.clinicaltrials.gov under NCT identifier NCT05504837.
+Added: KB407 was well tolerated with only mild to moderate and transient adverse events observed.
In January 2025, the CFF Therapeutic Development Network (“TDN”) Clinical Research Executive Committee granted full sanctioning of our KB407 Phase 1 CORAL-1 study protocol.
+Added: In January 2026, we announced a positive interim clinical update from Cohort 3, the highest dose cohort of CORAL-1, confirming the successful lung delivery and expression of wild-type CFTR protein following inhaled administration of KB407.
+Added: KB407 transduction was observed in all Cohort 3 patients with successful bronchoscopies irrespective of modulator-status and genetic background, with broad airway distribution and transduction as assessed by CFTR or viral marker immunofluorescence, ranging from 29.4% to 42.1%.
+Added: Consistent with the safety profile previously reported from Cohorts 1 and 2, inhaled KB407 continued to be well tolerated by patients treated with the highest dose in Cohort 3.
+Added: All but one KB407-related adverse event were mild to moderate in severity and transient in nature.
+Added: One serious adverse event (“SAE”) of asthma exacerbation was reported 24 hours after completion of the bronchoscopy and was deemed procedure related, and not related to KB407, by the independent data monitoring committee.
+Added: The SAE resolved in 5 days.
+Added: Details of the CORAL-1 study can be found at www.clinicaltrials.gov under NCT identifier NCT05504837.
+Added: We are now working with the TDN on a repeat dosing study design, CORAL-3, which was submitted to the FDA in December 2025.
+Added: CORAL-3 is designed to evaluate the safety and efficacy of repeat KB407 administration, including through regular assessments of lung function by spirometry, and to support potential registration.
+Added: We expect to align on the CORAL-3 study design with the FDA and start enrollment in the potentially registrational CORAL-3 study in the first half of 2026.
+Added: Additional details on the study design will be provided by the time of study initiation.
KB408 for Alpha-1 Antitrypsin Deficiency (“AATD”) Lung Disease
3 unchanged sentences
Low AAT serum levels can result in life threatening, progressive pulmonary impairment and severe respiratory insufficiency, manifesting as chronic obstructive pulmonary disease and panacinar emphysema.
−Removed: The lung degeneration observed in AATD patients derives from an unopposed, and therefore enhanced, neutrophil elastase (“NE”) activity, leading to an excessive degradation of elastin, collagen, and fibronectin.
+Added: The lung degeneration observed in AATD patients derives from unopposed, and therefore enhanced, neutrophil elastase (“NE”) activity, leading to an excessive degradation of elastin, collagen, and fibronectin.
The absence of proper NE inactivation by functional AAT ultimately results in lung tissue destruction, airway obstruction, and an increased inflammation state that compromises the integrity of the organ and contributes to an inadequate response to insults, including inefficient pulmonary bacterial clearance.
5 unchanged sentences
In small animal models, analysis of lung tissue biopsies, serum, and bronchoalveolar lavage fluid harvested 24 and 48 hours after inhalation of KB408 shows secretion of full-length AAT protein, with no evidence of significant or systemic toxicity.
−Removed: In September 2023, the FDA granted KB408 ODD for the treatment of AATD.
+Added: The FDA has granted KB408 ODD for the treatment of AATD.
Clinical Development of KB408
1 unchanged sentence
SERPENTINE-1 is a Phase 1 open-label, single dose escalation study in adult patients with AATD with a Pi*ZZ or Pi*ZNull genotype.
−Removed: In December 2024, we announced an interim clinical data update including safety data for seven patients enrolled in the first two dose escalation cohorts of SERPENTINE-1 as well as molecular data from two patients in the second cohort that had consented to bronchoscopy.
−Removed: Clear evidence of successful gene delivery and AAT expression was observed in both patients that underwent bronchoscopies, with the proportion of conducting airway epithelial cells positive for AAT increasing from 0% to 39% in one patient and from 3% to
−Removed: 35% in the other.
+Added: In December 2024, we announced an interim clinical data update including safety data for seven patients enrolled in the first two dose escalation cohorts of SERPENTINE-1 as well as molecular data from two patients in the second cohort (“Cohort 2”) that had consented to bronchoscopy.
+Added: Clear evidence of successful gene delivery and AAT expression was observed in both patients that underwent bronchoscopies, with the proportion of conducting airway epithelial cells positive for AAT increasing from 0% to 39% in one patient and from 3% to 35% in the other.
Secretion and functionality of encoded AAT was also demonstrated in the patient with available lavage samples, with AAT levels in epithelial lining fluid reaching 729 nM, and the proportion of free NE dropping from 97.2% to 40.2%, after a single KB408 dose.
KB408 was also found to be well-tolerated at both tested dose levels, with only mild to moderate and transient adverse events observed.
−Removed: Following this data update, we simultaneously expanded the second cohort and opened enrollment in the third and final cohort of SERPENTINE-1 for more comprehensive molecular assessments at both dose levels.
−Removed: We are working closely with the Alpha-1 Foundation and their Therapeutic Development Network on the SERPENTINE-1 study and expect to announce complete SERPENTINE-1 study results in the second half of 2025.
+Added: In August 2025, we confirmed SERPINA 1 delivery and functional AAT expression in a third patient dosed with KB408 in Cohort 2 and amended the SERPENTINE-1 protocol to investigate repeat dosing at the Cohort 2 dose level (the repeat dose cohort is referred to as “Cohort 2B”).
+Added: The first patient in Cohort 2B was dosed in August 2025 and enrollment in this repeat dose cohort is ongoing.
+Added: We expect to report interim safety and SERPINA1 delivery data from the repeat dose Cohort 2B in 2026.
+Added: Enrollment in single dose cohorts is now closed.
+Added: We are working closely with the Alpha-1 Foundation and their
+Added: Therapeutic Development Network on the SERPENTINE-1 study.
Details of the SERPENTINE-1 study can be found at www.clinicaltrials.gov under NCT identifier NCT06049082.
+Added: Ophthalmology
+Added: KB803 (Ophthalmic B-VEC) for Ocular Complications of DEB
+Added: Disease Background
+Added: DEB affects not only the skin, but also mucosal tissues that depend on COL7 anchoring fibrils to maintain epithelial lining integrity.
+Added: This includes the eye, where COL7 anchors the corneal epithelium.
+Added: For a meaningful proportion of DEB patients, the genetic defect in COL7A1 results in loss or malfunctioning of these anchoring fibrils causing ocular complications, such as corneal erosions, abrasions, blistering, and scarring, that can lead to progressive vision loss.
+Added: Over 50% of patients with the recessive form of DEB and an estimated 10% of patients with the dominant form of DEB are thought to suffer from ocular complications.
+Added: Correspondingly, we believe there are over 750 patients in the United States and over 2,000 worldwide that are affected.
+Added: Disease management varies from supportive care and wound management to surgical interventions to remove scar tissue.
+Added: No corrective or FDA approved therapies are presently available.
+Added: KB803 (Ophthalmic B-VEC)
+Added: KB803 is a redosable eye drop formulation of B-VEC, designed to deliver two copies of the COL7A1 transgene to the epithelial cells in a patient’s eye to produce COL7 protein.
+Added: As with VYJUVEK, the goal of therapy with KB803 is to treat the disease locally, at the molecular level, by providing the patient’s epithelial cells of the eye the template to make normal COL7 protein and thereby address the fundamental disease-causing mechanism.
+Added: In preclinical studies, single and repeated topical B-VEC administration to the eye in a mouse corneal lesion model resulted in localized COL7A1 expression with no adverse effects noted histologically.
+Added: B-VEC has been applied topically to the eye of one DEB patient under a compassionate use protocol.
+Added: The clinical observations of this compassionate use case were published in the New England Journal of Medicine in February 2024.
+Added: The patient presented with severe cicatrizing conjunctivitis secondary to DEB.
+Added: Surgical symblepharon lysis of the patient’s right eye with pannus removal was conducted and regular administration of B-VEC as an eye drop directly to the eye (5×10 9 PFU/mL) were added to routine post-surgical care, three times weekly for the first two weeks and then once weekly.
+Added: B-VEC application frequency was further decreased to once monthly once the corneal epithelium was healed.
+Added: B-VEC was well tolerated with no drug-related adverse events noted.
+Added: Full corneal healing was observed at three months, as well as significant visual acuity improvement from hand motion to 20/25 by eight months.
+Added: Clinical Development of KB803
+Added: In June 2025, we announced that we dosed the first patient in IOLITE, an intra-patient, double-blind, placebo-controlled, decentralized, multicenter Phase 3 registrational study with a crossover design to evaluate KB803 for the treatment and prevention of corneal abrasions in DEB patients, six months of age or older.
+Added: After observing a promising clinical safety profile in the initial patients treated with Krystal’s eye drop gene therapies, we modified the KB803 dosing schedule to reduce the potential impact of human error in eye drop administration.
+Added: Under the updated protocol, enrolled patients receive either a single eye drop of placebo or KB803, at a concentration of 10 9 PFU/mL, to each eye three times weekly for 12 weeks.
+Added: Drug administration is in the home setting and may be performed by a HCP or by the patient or their caregiver after receiving training on appropriate administration technique.
+Added: At the conclusion of the first 12 weeks, patients will be switched from placebo to KB803, or vice versa, and continue with three times weekly administration for a second 12 week period.
+Added: We expect to enroll approximately 16 patients in the IOLITE study.
+Added: The primary study endpoint is the change in the average number of days per month with corneal abrasion symptoms while receiving KB803 versus placebo.
+Added: Safety and secondary efficacy data, including weekly assessments of eye pain and monthly Epidermolysis Bullosa Eye Disease Index questionnaires, will be collected through to the end of the 24-week study period.
+Added: We continue to enroll patients in IOLITE and expect to complete enrollment in the first half of 2026 and report top-line results later in 2026.
+Added: More details of the IOLITE study can be found at www.clinicaltrials.gov under NCT identifier NCT07016750.
+Added: Patients seeking to participate in IOLITE must first enroll in an ongoing natural history study and complete a 12-week run-in period, during which they report the number of days that they experience symptoms of corneal abrasions.
+Added: Patients meeting the inclusion criteria following the 12-week run-in are eligible to participate in the IOLITE trial.
+Added: The natural history study was initiated in August 2024 and remains open for enrollment.
+Added: Details of the natural history study can be found at www.clinicaltrials.gov under NCT identifier NCT06563414.
+Added: KB801 for Neurotrophic Keratitis (“NK”)
+Added: Disease Background
+Added: NK is a rare, degenerative corneal disease characterized by damage or loss of function in the neurons innervating the eye leading to corneal epithelial defects, ulcers, and perforation.
+Added: Left untreated, NK can result in severe vision loss.
+Added: Although NK is a rare disease with an estimated prevalence in the range of 10 to 50 cases per 100,000, claims data analyses suggest awareness and diagnosis rates are on the rise in the United States.
+Added: Based on available claims data, an estimated 68,000 patients in the United States had a NK claim in 2024, up over 115% from 31,000 patients with a NK claim in 2020.
+Added: Recombinant nerve growth factor (“NGF”) eye drops have been shown to significantly improve corneal healing and are approved for the treatment of NK in multiple jurisdictions worldwide including the United States, but the short half-life of recombinant protein results in rapid clearance from the eye, thereby necessitating burdensome administration six times a day, and may lead to suboptimal treatment outcomes.
+Added: Eye pain during treatment is also frequently reported.
+Added: KB801 is an eye drop formulation of our novel HSV-1 based vector designed to deliver two transgene copies to the corneal epithelium for the sustained, localized expression and secretion of NGF and treatment of NK.
+Added: In preclinical studies presented at the Association for Research in Vision and Ophthalmology 2025 Annual Meeting in May 2025, KB801 was shown to efficiently transduce corneal epithelial cells in vitro and in vivo leading to sustained NGF production in the front of the eye.
+Added: By transducing the cells of the corneal epithelium to produce and secrete NGF, KB801 has the potential to significantly reduce the treatment burden for patients while also maintaining more consistent NGF levels in the front of the eye.
+Added: Clinical Development of KB801
+Added: In July 2025, we announced that we dosed the first patient in EMERALD-1, a Phase 1/2, randomized, double-masked, multicenter, placebo-controlled study evaluating KB801, administered as an eye drop, for the treatment of NK.
+Added: In October 2025, the FDA granted platform technology designation to the engineered HSV-1 viral vector used in KB801, a designation which affords development and manufacturing efficiencies for the development of KB801.
+Added: Following receipt of this designation, we amended the EMERALD-1 protocol to enable the study to serve as a registrational trial supporting the potential registration of KB801.
+Added: Under the updated protocol, we expect to enroll approximately 60 adult patients with Stage 2 or Stage 3 NK, as defined by the Mackie criteria.
+Added: Enrolled patients are randomized 1:1 to receive either KB801, at a concentration of 10 10 PFU/mL, or placebo topically to the study eye daily for eight weeks.
+Added: Drug administration may be performed either by a HCP or by the patient or their caregiver at home after receiving training on appropriate administration technique.
+Added: The KB801 dosing schedule was modified taking into consideration the potential to reduce the impact of human error in eye drop administration at home and the promising clinical safety profile in the initial patients treated with KB801 and KB803.
+Added: The primary objectives of EMERALD-1 are to evaluate the safety and efficacy of topical ocular administration of KB801 for the treatment of NK.
+Added: The primary efficacy assessment is the proportion of patients with complete durable healing of corneal epithelium at eight weeks.
+Added: Additional exploratory efficacy measures will include change in corneal lesion size from baseline, each assessed at weeks 4, 6, 8, and 10, as well as evaluations of corneal sensation and patient-reported symptom burden.
+Added: Enrollment in EMERALD-1 is ongoing, and we expect to report top-line data in 2026.
+Added: More details of the EMERALD-1 study can be found at www.clinicaltrials.gov under NCT identifier NCT06999733.
+Added: KB111 for Hailey-Hailey Disease (“HHD”)
+Added: Disease Background
+Added: HHD is a serious and rare monogenic skin disorder characterized by painful rash and blistering in skin folds and linked to low expression of levels human calcium transporter ATPase type 2C member 1 (“ATP2C1”) in keratinocytes.
+Added: Patients with HHD report debilitating symptoms of pain, itch, burning, infections, and body odor, as well severe, negative impacts on quality of life and psychological distress.
+Added: The prevalence of HHD is not well characterized and is most commonly estimated at roughly 1 per 50,000, although underreporting is possible.
+Added: Current disease management is supportive in nature and no specific therapy for HHD has been approved by the FDA or EMA.
+Added: KB111 is a topical gel formulation of our novel vector designed to deliver two copies of the full-length, wild-type ATP2C1 transgene to skin cells for the treatment of HHD.
+Added: In preclinical studies presented at the Society for Investigative Dermatology 2025 Annual Meeting in May 2025, KB111 was shown to efficiently deliver ATP2C1 to keratinocytes in vitro and in vivo resulting in increased expression of functional ATP2C1.
+Added: By increasing functional ATP2C1 levels in the skin, KB111 has the potential to accelerate lesion healing and meaningfully reduce disease burden for HHD patients.
+Added: In January 2026, the FDA granted KB111 FTD for the treatment of HHD.
+Added: Clinical Development of KB111
+Added: In October 2025, the FDA cleared our investigational new drug (“IND”) application to evaluate KB111 in the clinic.
+Added: We are currently developing an HHD-specific evaluation scale necessary for the clinical evaluation of KB111.
+Added: We expect to complete development and validation of the scale in the first half of 2026 and initiate a registrational, intra-patient randomized, double-blind, placebo-controlled, multi-center study evaluating KB111 for the treatment of HHD in the second half of 2026.
KB707 for Solid Tumors
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Of these, an estimated five million deaths were attributed to solid tumor malignancies of the lung, colon and rectum, liver, stomach, and breast alone.
−Removed: Solid tumor malignancies similarly impose a heavy burden on patients in the United States, with the National Cancer Institute estimating that over 300,000 patients will have died from lung, colon and rectum, pancreas, breast, prostate, liver and bile duct, and melanoma of the skin cancers in 2023.
+Added: Solid tumor malignancies similarly impose a heavy burden on patients in the United States, with the National Cancer Institute estimating that hundreds of thousands of patients died from lung, colon and rectum, pancreas, breast, prostate, liver and bile duct, and melanoma of the skin cancers in 2025.
+Added: There is an especially urgent need for new therapies for the treatment of lung cancer, which is widely considered the deadliest cancer globally and in the United States.
+Added: Even with currently available therapies, the National Cancer Institute estimates that over 124,000 patients died from lung cancer in 2025.
KB707 is a redosable, immunotherapy designed to deliver genes encoding both human interleukin-2 (“IL-2”) and interleukin-12 (“IL-12”) to the tumor microenvironment and promote systemic immune-mediated tumor clearance.
8 unchanged sentences
Both intratumoral and inhaled KB707 have also been granted RPDD by the FDA, with intratumoral KB707 receiving RPDD for the treatment of rhabdomyosarcoma in August 2024 and inhaled KB707 receiving RPDD for the treatment of osteosarcoma in May 2024.
+Added: In February 2026, the FDA also granted RMAT designation to KB707 for the treatment of advanced or metastatic NSCLC.
+Added: We have prioritized development of the inhaled KB707 formulation based on early clinical evidence of efficacy for the treatment of NSCLC.
Clinical Development of Inhaled KB707
−Removed: In January 2024, the FDA accepted an amendment to our KB707 investigational new drug (“IND”) application to evaluate inhaled KB707 in a clinical trial to treat patients with locally advanced or metastatic solid tumors of the lung.
+Added: In January 2024, the FDA accepted an amendment to our KB707 IND application to evaluate inhaled KB707 in a clinical trial to treat patients with locally advanced or metastatic solid tumors of the lung.
The study, KYANITE-1, is an open-label, multi-center, dose escalation and expansion Phase 1/2 study, evaluating inhaled KB707, as monotherapy or in combination, in patients with advanced solid tumor malignancies affecting the lungs, who relapsed or are refractory to standard of care.
−Removed: The primary objective of the study is to evaluate safety and tolerability of KB707 delivered via
−Removed: inhalation, alone or in combination.
+Added: The primary objective of the study is to evaluate safety and tolerability of KB707 delivered via inhalation, alone or in combination.
Efficacy is also being assessed by multiple measures, including objective response rate (“ORR”), as are the immune effects of KB707 monotherapy.
1 unchanged sentence
In August 2024, the monotherapy dose escalation portion of the study was completed, and the monotherapy dose expansion cohort was opened.
−Removed: In December 2024, we announced an initial clinical update for the monotherapy dose escalation and expansion cohorts, including safety data for 37 patients that had received at least one dose of inhaled KB707 and efficacy data from 11 patients with advanced non-small cell lung cancer (“NSCLC”) evaluable for response with at least one radiographic scan and RECIST v1.1 evaluation.
+Added: In December 2024, we announced an initial clinical update and early evidence of monotherapy activity from the monotherapy dose escalation and expansion cohorts of KYANITE-1.
+Added: The data update included safety data for 37 patients that had received at least one dose of inhaled KB707 and efficacy data from 11 patients with advanced NSCLC evaluable for response with at least one radiographic scan and RECIST v1.1 evaluation.
Patients included in the efficacy analysis were heavily pre-treated with four median lines of prior therapy and all had received at least one line of prior immunotherapy.
−Removed: In this NSCLC patient analysis cohort, as of data cut-off, an ORR of 27%, with three partial responses, was achieved.
+Added: In this NSCLC patient cohort, as of data cut-off, an ORR of 27%, with three partial responses, was achieved.
The disease control rate (“DCR”) was 73% with 7 out of 11 patients still remaining on treatment.
2 unchanged sentences
The majority of treatment-related adverse events were mild to moderate in severity and transient, with no Grade 4 or 5 adverse events observed.
−Removed: Building on promising initial monotherapy data, KYANITE-1 was amended to add two dose expansion cohorts evaluating inhaled KB707 in combination with anti-PD-1 therapy or anti-PD-1 therapy and chemotherapy in patients with advanced NSCLC.
−Removed: Enrollment in both cohorts is ongoing.
+Added: Based on these positive initial results, we also announced, in December 2024, the amendment of KYANITE-1 to include additional cohorts for the evaluation of inhaled KB707 in combination.
+Added: In June 2025, we disclosed a clinical update from the monotherapy dose escalation and expansion cohorts of KYANITE-1, including updated efficacy data from the previously disclosed cohort of 11 evaluable patients with heavily pre-treated advanced NSCLC.
+Added: As of the updated data cutoff, the ORR in the NSCLC patient cohort was 36%.
+Added: The DCR was 54%.
+Added: Median duration of response and progression free survival were not reached.
+Added: Inhaled KB707 was again found to be safe and generally well tolerated as monotherapy in the 39 patients included in the safety analysis, with the majority of treatment-related adverse events deemed mild to moderate in severity and transient and no Grade 4 or 5 adverse events observed.
+Added: In August 2025, we were granted an End of Phase 2 meeting with the FDA to discuss the inhaled KB707 program and, in November 2025, we announced that based on the FDA’s feedback, we expect that a single Phase 3 registrational study, evaluating inhaled KB707 in combination with chemotherapy against chemotherapy alone in patients with advanced NSCLC, would be sufficient to support potential registration of inhaled KB707 in combination with chemotherapy as a second-line treatment for NSCLC.
+Added: In support of this potential registrational pathway, we opened a new cohort in KYANITE-1 to evaluate inhaled KB707 in combination with chemotherapy in patients with advanced NSCLC.
+Added: Enrollment in the new cohort of KYANITE-1 evaluating inhaled KB707 in combination with chemotherapy is ongoing, and we expect to report interim efficacy data and potential registrational study plans in 2026.
Details of the KYANITE-1 study can be found at www.clinicaltrials.gov under NCT identifier NCT06228326.
6 unchanged sentences
OPAL-1 was subsequently amended to add two dose expansion cohorts, in addition to the monotherapy dose expansion cohort, evaluating intratumoral KB707 in combination with anti-PD-1 and anti-lymphocyte activation gene 3 therapy or anti-PD-1 therapy alone, in patients with advanced melanoma that is relapsed or refractory to standard of care.
−Removed: Evaluation of intratumoral KB707 as monotherapy and in combination is ongoing.
+Added: In August 2025, we announced that we were prioritizing the development of inhaled KB707 for the treatment of NSCLC and had paused enrollment in OPAL-1.
+Added: We continue to follow patients enrolled in OPAL-1 and based on safety and efficacy results from the study, we may adjust development plans for intratumoral KB707.
Details of the OPAL-1 study can be found at www.clinicaltrials.gov under NCT identifier NCT05970497.
−Removed: KB105 for TGM1-Deficient Lamellar Ichthyosis (“LI”)
−Removed: Disease Background
−Removed: LI is a form of autosomal recessive congenital ichthyosis (“ARCI”) and a life-long, severe monogenic skin disease.
−Removed: While a number of genetic mutations have been associated with the development of ARCI and LI, the most common cause is an inactivating mutation in the human TGM1 gene encoding the enzyme transglutaminase-1 (“TGM1”), a protein that is essential for the proper formation of the skin barrier.
−Removed: Mutations in the TGM1 gene, and the subsequent disruption to the epidermal barrier, leads to pronounced dehydration, trans-epidermal exposure to unwanted toxins and surface microorganisms, and a greatly increased risk of infection.
−Removed: TGM1 deficiency is associated with increased mortality in the neonatal period and has a dramatic impact on quality of life.
−Removed: Patients suffering from LI often exhibit life-long pronounced plate-like scaling of the skin, which is often of a dark color and can cover the whole body.
−Removed: Such patients frequently suffer from exposure of the inner eyelid surface due to turning away of the eyelids from the eye (ectropion), the turning outwards of the lips (eclabium), deformities of joint and nasal cartilage (hypoplasia), scarring alopecia and a thickening of the skin on the palms of the hands and soles of the feet (palmoplantar keratoderma).
−Removed: Additional complications can include episodes of sepsis, fluid and electrolyte imbalances due to impaired skin barrier function, and failure to thrive, especially during the neonatal period and infancy.
−Removed: Severe heat intolerance and nail dystrophy are also frequently observed.
−Removed: There are currently no treatments targeting molecular correction of this disease.
−Removed: We estimate there are approximately 2,000 to 5,000 patients with TGM1-deficient LI in the United States and Europe.
−Removed: KB105 is a redosable, off the-shelf gene therapy designed to deliver two copies of the TGM1 gene when applied topically, directly to a patient’s exfoliated skin.
−Removed: The goal of direct supplementation of TGM1 protein at the site of administration is local correction and phenotypic improvement.
−Removed: Like B-VEC, KB105 was designed to be easily administered by a healthcare professional in the doctor’s office or, potentially, at the patient’s home.
−Removed: The FDA and the EMA have each granted KB105 ODD and Orphan Designation, respectively, for the treatment of TGM1-ARCI, and the FDA has granted KB105 Fast Track Designation and RPDD for the treatment of TGM1-ARCI.
−Removed: Clinical Development of KB105
−Removed: In September 2019, we initiated a Phase 1/2 trial, JADE-1, in TGM1-deficient ARCI patients.
−Removed: In May 2020, initial clinical data from the Phase 1 portion of the study which enrolled adult patients were presented at the Society for Investigative Dermatology (“SID”) meeting.
−Removed: In August 2020, we initiated the second phase of our Phase 2 portion of the clinical trial of KB105 to treat ARCI.
−Removed: We enrolled one patient in whom four rectangular 100cm 2 (4-inch x 4-inch) areas of skin were selected as Target Areas (“TAs”).
−Removed: Each treatment area was assigned to receive repeat doses of 4.0x10 9 PFU (n=2 treatment areas) or 1.0x10 10 PFU (n=2 treatment areas).
−Removed: Each area was dosed on Day 1 and 3, after which dosing continued either every three days (n=2 treatment areas) or every six days (n=2 treatment areas) up to day 30.
−Removed: Treatment areas were clinically evaluated at pre- and post-KB105 application timepoints using a 5-point IGA scale (0 = clear;
−Removed: 1 = almost clear;
−Removed: 3 = moderate;
−Removed: 4 = very severe).
−Removed: In July 2021, we announced initial Phase 2 data.
−Removed: Repeated topical doses of KB105 were well tolerated, and no drug-related adverse effects were reported.
−Removed: No vector shedding or systemic viral exposure was detected at any time point.
−Removed: Improvement on the IGA scale was observed in each treatment area, with the maximum effect observed in TA3 and TA4 that received the highest dose;
−Removed: at day 27, the investigator assigned an IGA score of two, which was improved as compared to baseline score of four in each area.
−Removed: Variable 1-point improvements were observed at other time points and in the treatment areas that received the lowest dose.
−Removed: As in the Phase 1 portion of the trial, TGM1 turnover was observed to be variable but relatively rapid, and the observed IGA improvements were not sustained through day 60.
−Removed: We plan to initiate the Phase 2 portion of the JADE-1 trial evaluating KB105 for the treatment of TGM1-deficient LI in pediatric patients in 2026.
−Removed: Details of the JADE-1 study can be found at www.clinicaltrials.gov under NCT identifier NCT04047732.
−Removed: While our focus is on the development of gene therapies to treat patients with severe, life‑threatening, or rare diseases with high unmet medical needs, we are also evaluating the potential of our platform to address more prevalent and/or non-genetic conditions.
−Removed: To that end, in April 2019, we incorporated Jeune Aesthetics, a wholly-owned subsidiary, for the purposes of undertaking preclinical and clinical studies for aesthetic skin conditions.
+Added: While our focus is on the development of gene therapies to treat patients with severe, life‑threatening, or rare diseases with high unmet medical needs, we are also evaluating the potential of our platform to address aesthetic conditions.
+Added: We incorporated Jeune Aesthetics, a wholly-owned subsidiary, for the purposes of undertaking preclinical and clinical studies for aesthetic skin conditions.
KB304 for Dynamic Wrinkles of the Décolleté
1 unchanged sentence
These fibrils provide strength to the skin and are critical for the maintenance of skin tissue architecture.
+Added: In the skin, new collagen synthesis is affected by the deposition of, and complex interactions between, COL1 and COL3.
+Added: COL3 appears early during collagen fibril formation and has been shown to both regulate the dimensions of COL1 fibers and enhance COL1 elasticity.
Many characteristics of skin aging are largely due to aberrant collagen homeostasis, including reduced collagen biosynthesis, increased collagen fibril fragmentation, and progressive loss of dermal collagen culminating in a net collagen deficiency, resulting from both intrinsic (e.g., passage of time, genetics) and extrinsic (e.g., chronic light exposure, pollution) pressures.
These factors together lead to cumulative structural and physiological alterations to the skin, ultimately leading to the onset and eventual worsening of skin wrinkles.
−Removed: Skin rejuvenation is the process of reversing or repairing irregularities in the skin and is achieved, in part, by the synthesis of new collagen (neocollagenesis).
−Removed: In the skin, neocollagenesis is affected by the deposition of, and complex interactions between, COL1 and COL3.
−Removed: COL3 appears early during collagen fibril formation and has been shown to both regulate the dimensions of COL1 fibers and enhance COL1 elasticity.
+Added: Elastin (“ELN”) is the major constituent of elastic fibers which provides resilience and elasticity to tissues and organs and, as such, is another important determinant of skin tissue architecture.
+Added: Although ELN represents only 2% of total dermal protein, it is roughly 1,000-fold more flexible than collagen, and thus, is the main component providing elasticity to skin.
+Added: ELN synthesis occurs early in life and through childhood, after which very little turnover is observed unless the elastic fibers are subject to injury.
+Added: Although elastin is a durable biopolymer that does not turn over appreciably in healthy tissue, aging of elastin is observed over time as damage to elastic fibers increases susceptibility to enzymatic degradation.
+Added: Elastin aging is induced and accelerated by environmental influences, primarily UV radiation.
+Added: UV-induced extrinsic aging leads to, among other defects, loss of elasticity.
+Added: Skin rejuvenation is the process of reversing or repairing irregularities in the skin and is achieved, in part, by the synthesis of new collagen and ELN.
Significant consumer demand exists for fundamentally rejuvenative aesthetic products, including among younger consumers that are seeking more preventative interventions to maintain a natural-looking, youthful appearance.
−Removed: Demand is expected to grow driven by increasing aesthetic injectable adoption in emerging markets and shifting consumer attitudes about wellness, beauty, and healthy aging that have increased awareness and acceptance of aesthetic treatments among new consumer segments.
+Added: This demand is expected to grow driven by increasing aesthetic injectable adoption in emerging markets and shifting consumer attitudes about wellness, beauty, and healthy aging that have increased awareness and acceptance of aesthetic treatments among new consumer segments.
One area of the skin that can experience early aging is the female décolleté (upper chest).
1 unchanged sentence
The female décolleté is considered an extension of the face and demand for aesthetic solutions is high, yet there are no FDA-approved aesthetic injectable products for the décolleté, and aesthetic procedures for the delicate skin of the décolleté are challenging and can cause hyperpigmented and hypopigmented skin.
−Removed: KB301 leverages our clinical experience in delivering genes of interest to the skin and is designed to stimulate biorejuvenation of the skin via delivery of two copies of a COL3A1 transgene that encodes for COL3.
+Added: KB304 leverages our clinical experience in delivering genes of interest to the skin and is designed to stimulate biorejuvenation of the skin via delivery of both COL3A1 and ELN transgenes encoding full-length human COL3 and ELN.
KB304 is administered via intradermal injection.
−Removed: We believe that our approach of directed expression of full-length human COL3 via intradermal application of KB301 provides a unique and straightforward approach to restoring collagen homeostasis, and by extension, reconstructing an optimal physiologic environment in the skin to treat wrinkles or other presentations of aged or damaged skin.
+Added: We believe that our approach of directed expression of full-length human COL3 and ELN via intradermal application of KB304 provides a unique, comprehensive, and straightforward approach to restoring collagen homeostasis and skin elasticity, and by extension, reconstructing an optimal physiologic environment in the skin to treat wrinkles or other presentations of aged or damaged skin.
Clinical Development of KB304
+Added: In November 2024, we dosed the first subject in PEARL-2, a 2:1 randomized, double-blind, placebo-controlled Phase 1 study evaluating KB304, for the treatment of wrinkles of the décolleté, In July 2025, we announced positive safety and efficacy results from PEARL-2, including significant improvements in key skin aesthetic attributes such as wrinkles and elasticity.
+Added: Meaningful aesthetic improvements in multiple skin attributes were reported by the investigator and subjects alike following KB304 treatment, with clear and statistically significant advantages over placebo.
+Added: Improvements were reported not only for wrinkles but also multiple additional skin attributes, including elasticity, crepiness, hydration, and radiance.
+Added: Increased subject satisfaction with wrinkle appearance was also reported, with clear separation from placebo.
+Added: All adverse events were mild-to-moderate in severity and transient.
+Added: The frequency and duration of adverse events also decreased with subsequent doses of KB304.
+Added: No serious or severe adverse events were reported.
+Added: Details of the study can be found at www.clinicaltrials.gov under NCT identifier NCT06724900.
+Added: Based on the broad aesthetic improvements observed following KB304 treatment in PEARL-2, we are progressing KB304 into a Phase 2 study for the treatment of wrinkles of the décolleté.
+Added: In support of the Phase 2 study, we developed and validated a décolleté-specific photonumeric scale (“JDWS”) which was submitted to the FDA in the second half of 2025.
+Added: We have aligned with the FDA on the JDWS and expect to initiate the Phase 2 study in 2027.
+Added: Additional Pipeline Product Candidates for Aesthetic Skin Conditions Including KB301
+Added: In addition to KB304, we are advancing a pipeline of aesthetic product candidates targeting the loss or reduced expression of individual structural proteins of the skin to address specific skin attributes and aesthetic skin conditions.
+Added: Of these, the most advanced candidate is KB301, a solution formulation of our novel vector for intradermal injection designed to deliver two copies of the COL3A1 transgene to address signs of aging or damaged skin caused by declining levels of, or damaged proteins within the extracellular matrix, including type III collagen.
+Added: Clinical Development of KB301
We initiated a Phase 1 clinical trial, the PEARL-1 trial, for the treatment of aesthetic skin conditions in August 2020.
1 unchanged sentence
KB301 was well tolerated, and we were able to biopsy and demonstrate proof-of-mechanism.
−Removed: Complete results from Cohort 1 focused on safety were presented at the 2021 SID Annual Meeting.
+Added: Complete results from Cohort 1 focused on safety were presented at the 2021 Society for Investigative Dermatology Annual Meeting.
In March 2022, we announced positive proof-of-concept efficacy and safety data from Cohort 2 of the PEARL-1 study of KB301 for the treatment of aesthetic skin indications.
11 unchanged sentences
In November 2022, we announced nine-month durability of effect in Cohort 2 of the PEARL-1 study of KB301.
−Removed: Building on the results from Cohort 2, we opened two additional open-label, single-arm PEARL-1 cohorts to evaluate KB301 in two potential target indications for Phase 2, lateral canthal lines at rest and dynamic wrinkles of the décolleté, referred to as Cohorts 3 and 4, respectively.
+Added: Building on the results from Cohort 2, we opened two additional open-label, single-arm PEARL-1 cohorts to evaluate KB301 in two potential target indications for a Phase 2 trial, lateral canthal lines at rest and dynamic wrinkles of the décolleté, referred to as Cohorts 3 and 4, respectively.
In August 2024, we announced positive interim safety and efficacy results from both cohorts, assessed out to two months following KB301 injections.
4 unchanged sentences
No drug related serious adverse events were reported.
−Removed: Based on these Phase 1 results, we have selected treatment of the dynamic wrinkles of the décolleté for advanced clinical development and initiated development of a décolleté-specific evaluation scale.
−Removed: We expect to complete scale development and dose the first subject in a randomized, placebo-controlled Phase 2 study evaluating KB301 for the treatment of dynamic wrinkles of the décolleté in the second half of 2025.
Details of the PEARL-1 study can be found at www.clinicaltrials.gov under NCT identifier NCT04540900.
−Removed: KB304 for Aesthetic Skin Conditions
−Removed: Elastin is a key connective tissue protein and the major constituent of elastic fibers which provides resilience and elasticity to tissues and organs.
−Removed: It represents only 2% of total dermal protein;
−Removed: however, it is roughly 1,000-fold more flexible than collagen, and thus, is the main component providing elasticity to skin.
−Removed: Elastin synthesis occurs early in life and through childhood, after which very little turnover is observed unless the elastic fibers are subject to injury.
−Removed: Although elastin is a durable biopolymer that does not turn over appreciably in healthy tissue, aging of elastin is observed over time as damage to elastic fibers increases susceptibility to enzymatic degradation.
−Removed: Elastin aging is induced and accelerated by environmental influences, primarily UV radiation.
−Removed: UV-induced extrinsic aging leads to, among other defects, loss of elasticity.
−Removed: In aged skin where elasticity loss is especially pronounced, elastin replenishment in conjunction with neocollagenesis could yield profound aesthetic improvements.
−Removed: KB304 is designed to stimulate biorejuvenation of the skin via delivery of both COL3A1 and ELN transgenes encoding full-length human COL3 and elastin.
−Removed: KB304 is administered via intradermal injection.
−Removed: We believe that the combination of COL3 and elastin could provide additional aesthetic benefits over collagen replenishment alone in aged skin where elasticity loss is especially prominent.
−Removed: Clinical Development of KB304
−Removed: In November 2024, we dosed the first subject in our ongoing, randomized and placebo-controlled Phase 1 PEARL-2 study evaluating KB304 for the treatment of wrinkles.
−Removed: We expect to enroll up to 21 subjects in PEARL-2, randomized 2:1 to KB304 or placebo, and report top-line results from the study in the second half of 2025.
−Removed: Details of the PEARL-2 study can be found at www.clinicaltrials.gov under NCT identifier NCT06724900.
+Added: We are currently evaluating aesthetic indications most suitable for advanced clinical development of KB301.
Future Opportunities
1 unchanged sentence
Research focus areas include the development of new candidates for the treatment of additional monogenic rare diseases in the skin, lung, and eye, as well as exploration of new routes of administration to treat diseases in additional tissues.
−Removed: We also believe the ability to redose, as well as the large payload capacity of our proprietary vectors, will allow us to deliver multiple genes and other effectors, which could enable development of therapies for more common conditions that are not necessarily the result of an inherited genetic defect, such as KB707.
−Removed: As additional proof-of concept we have generated a library of vectors designed to deliver anti-inflammatory antibodies.
−Removed: Further, we evaluated one of these vectors in an animal model of atopic dermatitis where expression of the vector-encoded-antibody was confirmed, and efficacy was observed.
+Added: We also believe the ability to redose, as well as the large payload capacity of our proprietary vectors, will allow us to deliver multiple genes and other effectors, which could enable development of therapies for more common conditions that are not necessarily the result of an inherited genetic defect.
If we are able to successfully generate product candidates to treat these more common conditions, we intend to seek collaborative alliances towards the development and potential commercialization of these therapies.
1 unchanged sentence
In-House CGMP Facilities
−Removed: We have built in-house CGMP facilities to enable better quality control, shorten lead times, lower costs and strengthen command over our intellectual property.
+Added: We have built in-house CGMP facilities in the United States to enable better quality control, shorten lead times, lower costs and strengthen command over our intellectual property.
Our first facility, ANCORIS, a commercial-scale CGMP-compliant manufacturing facility, is producing VYJUVEK for commercial sales.
In December 2022, the FDA completed a successful audit of our ANCORIS facility.
−Removed: In February 2024, the EMA completed inspection of our ANCORIS facility as part of the MAA review process and, in May 2024, EU GMP certification was granted by the EMA.
+Added: In February 2024, the EMA completed inspection of our ANCORIS facility as part of the marketing authorization application review process and, in May 2024, European Union good manufacturing practice certification was granted by the EMA.
+Added: ANCORIS has also passed inspection by Japanese regulatory authorities as part of the Japanese New Drug Application review process in 2025.
Our second commercial scale CGMP facility, ASTRA, was completed and qualified in 2023.
2 unchanged sentences
Our proprietary manufacturing process which was initially developed for B-VEC and is now being used across our platform, was developed and optimized internally and involves both an upstream production process and downstream purification process.
−Removed: Recombinant viral vectors are rendered incapable of, or attenuated for, replacing in human cells by removal of specific viral machinery, including packaging proteins.
+Added: Recombinant viral vectors are rendered incapable of, or attenuated for, replication in human cells by removal of specific viral machinery, including packaging proteins.
However, to produce the recombinant virus, these viral proteins have to be re-introduced into the virus production process so that the viral vector can be packaged.
2 unchanged sentences
The difficulty of this approach is that it requires c-scale manufacturing and qualification of each of the packaging plasmids and optimization of the transfection method.
−Removed: Even with optimized reagents and methods, significant batch-to-batch variability is seen in viral vector yield and titer that, we believe, drives up the cost of viral vector manufacturing and scale-up and increases the risk of failure during manufacturing.
−Removed: Our proprietary upstream process for HSV-1 production avoids the aforementioned issues.
+Added: Even with optimized reagents and methods, other viral vector production systems exhibit significant batch-to-batch variability in viral vector yield and titer that, we believe, drives up the cost of viral vector manufacturing and scale-up and increases the risk of failure during manufacturing.
+Added: Our proprietary upstream production process avoids the aforementioned issues.
Our process requires three critical components:
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Optimization of MCB, MVSS and production methods requires extensive knowledge and technical experience with the HSV-1 genome and significant upfront effort to design and select the best virus seed stock and complementing cell line.
−Removed: We have screened hundreds of cell line clones to find the best complementing cell lines, and similarly designed and generated the optimal virus seed stocks for VYJUVEK and each of our product candidates.
+Added: We have screened hundreds of cell line clones to find the best complementing cell lines and designed and generated the optimal virus seed stocks for VYJUVEK and each of our product candidates.
The viral seed stock expresses the therapeutic proteins under the control of strong constitutive or tissue-specific promoters and additional non-coding regulatory sequences have been included to optimize gene expression.
1 unchanged sentence
Unlike the upstream process, steps used to purify and concentrate the viral vector product are often common across different viral vector platforms and usually involve multiple stages of purification, clarification, concentration, and diafiltration, with the ultimate goal to remove contaminants and concentrate the product.
−Removed: We have developed a robust and reproducible process for purifying our viral vector to required concentrations for commercial and clinical use, while successfully removing contaminants to meet FDA guidelines.
+Added: We have developed a robust and reproducible process for purifying our viral vector to required concentrations for commercial and clinical use, while successfully removing contaminants to meet FDA and other regulatory guidelines.
We believe that the MVSS and MCB are a vital part of the production of VYJUVEK and our product candidates, as they ensure the reproducible production of multiple commercial and clinical batches in a short six-week cycle time frame and in a cost-effective manner.
−Removed: We have made significant investments in developing the most comprehensive and optimized manufacturing process for VYJUVEK and our vector product candidates, including:
+Added: We have made significant investments in developing the most comprehensive and optimized manufacturing process for VYJUVEK and our product candidates, including:
• A proprietary vector manufacturing technique and a series of high-efficiency purification processes that produce highly purified therapeutic vectors and can be adapted for each product candidate;
−Removed: • A critical list of CGMP assays to accurately characterize our process and the HSV-1 vectors we produce.
+Added: • A critical list of CGMP assays to accurately characterize our process and the HSV-1-based vectors we produce.
The biotechnology and pharmaceutical industries are highly competitive.
4 unchanged sentences
Dystrophic Epidermolysis Bullosa
−Removed: A number of companies are developing drug candidates for the treatment of DEB.
−Removed: VYJUVEK is the only corrective therapy for DEB approved worldwide.
+Added: A number of companies are developing or commercializing drug candidates for the treatment of DEB.
+Added: VYJUVEK is the first corrective therapy for DEB approved worldwide.
We believe our competitors fall into two broad categories:
• Corrective Approaches:
−Removed: We are aware of two companies, Abeona Therapeutics Inc.
−Removed: and Castle Creek Biosciences, Inc., which are developing autologous or grafting gene therapy approaches to treating DEB.
+Added: We are aware of companies, Abeona Therapeutics Inc.
+Added: and Castle Creek Biosciences, Inc., which are developing or have commercialized autologous or grafting gene therapy approaches to treating DEB.
+Added: Abeona Therapeutics Inc.’s autologous gene therapy product Zevaskyn ® (prademagene zamikeracel) was approved by the FDA in 2025.
We are also aware of a recombinant-protein-based approach being developed by BridgeBio Pharma, Inc.’s affiliate company, Phoenix Tissue Repair.
1 unchanged sentence
We are aware of companies, such as Chiesi Farmaceutici S.p.A.
−Removed: and RHEACELL GmbH & Co., which are developing product candidates taking a palliative approach to treating the disease.
−Removed: Chiesi Farmaceutici S.p.A.’s palliative treatment Filsuvez ® (birch triterpenes) was approved by the FDA in the United States in 2023 and was previously approved by the EMA for the EU.
−Removed: Ophthalmology
−Removed: Ocular Complications Secondary to Dystrophic Epidermolysis Bullosa
−Removed: There are no approved therapies for ocular complications secondary to DEB at this time.
−Removed: We are aware of Eliksa Therapeutics’ program evaluating amniotic fluid derived ELK-003 eye drops to treat corneal abrasions in individuals with epidermolysis bullosa.
+Added: and RHEACELL GmbH & Co., which are developing or have commercialized products taking a palliative approach to treating the disease.
+Added: Chiesi Farmaceutici S.p.A.’s palliative treatment Filsuvez ® (birch triterpenes) was approved by the FDA in 2023 and was previously approved by the EMA.
Cystic Fibrosis
There are no approved therapies for CF patients ineligible or intolerant to modulator regiments.
−Removed: We are aware of several preclinical or early clinical stage nucleic-acid-based programs for treatment of this patient population including Vertex Pharmaceuticals Inc., ReCode Therapeutics, Inc., Spirovant Sciences, Inc., and 4D Molecular Therapeutics, Inc.
+Added: We are aware of several preclinical or early clinical stage nucleic-acid-based programs for treatment of this patient population including programs at Vertex Pharmaceuticals Inc., ReCode Therapeutics, Inc., Spirovant Sciences, Inc., and 4D Molecular Therapeutics, Inc.
Alpha-1 Antitrypsin Deficiency
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and Beam Therapeutics Inc., which are developing gene editing therapies inhibitors to treat both the lung and liver manifestations of AATD.
+Added: Ophthalmology
+Added: Ocular Complications of DEB
+Added: There are no approved therapies for ocular complications secondary to DEB at this time.
+Added: We are aware of Eliksa Therapeutics’ program evaluating amniotic fluid derived ELK-003 eye drops to treat corneal abrasions in individuals with epidermolysis bullosa.
+Added: Neurotrophic Keratitis
+Added: We are aware of companies, such as Dompé farmaceutici S.p.A., which are developing or have commercialized product candidates for the treatment of NK.
+Added: Dompé farmaceutici S.p.A,’s Oxervate ® (cenegermin) was approved by the FDA in 2018 and by the EMA in 2017.
+Added: Hailey-Hailey Disease
+Added: There are no approved therapies for HHD at this time.
+Added: We are aware of an investigator-initiated study evaluating Johnson & Johnson’s Tremfya ® (guselkumab) for the treatment of HHD, and a previously completed investigator initiated study evaluating botulinum toxin for the treatment of HHD.
A large number of companies are focused on the development and commercialization of new therapeutics for the treatment of locally advanced or metastatic tumors.
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Some of the most established companies in the marketing and development of new cancer drugs include Merck & Co Inc., Bristol Myers Squibb Company, Johnson & Johnson, and Pfizer Inc.
−Removed: Lamellar Ichthyosis
−Removed: There are no approved therapies for LI at this time.
−Removed: We are aware that LEO Pharma A/S has recently completed a clinical trial of a product for the treatment of congenital ichthyosis.
Aesthetic Skin Conditions
6 unchanged sentences
However, trade secrets can be difficult to protect.
−Removed: In addition to patent protection, regulatory exclusivity, and trade secret protection, we also protect our approved product, product candidates
−Removed: and platform technology with trademarks and contractual protections.
+Added: In addition to patent protection, regulatory exclusivity, and trade secret protection, we also protect our approved product, product candidates and platform technology with trademarks and contractual protections.
Additionally, we seek to protect our proprietary technology and processes, and obtain and maintain ownership of certain technologies, in part, through confidentiality agreements and intellectual property assignment agreements with our employees, consultants and commercial partners.
2 unchanged sentences
These patent applications are directed to various inventions.
−Removed: We do not have patents or patent applications in every jurisdiction where there is a potential commercial market for our approved product or our product candidates.
+Added: We do not have patents or patent applications in every jurisdiction where there is a potential commercial market for
+Added: our approved product or our product candidates.
For each of our programs, our decision to seek patent protection in specific foreign markets, in addition to the United States, is based on many factors, including:
35 unchanged sentences
12/28/2036 Krystal
+Added: AU 2022204729 Australia Methods of Use – Methods of use of replication-defective HSV vectors for delivering any effector to skin-targeted therapeutics
+Added: 12/28/2036 Krystal
+Added: AU 2025200334 Australia Composition of Matter & Methods of Use – Delivery platform for targeted therapeutics, as well as methods of its use for delivering any effector to the skin
+Added: 12/28/2036 Krystal
+Added: NZ 778381 New Zealand Composition of Matter & Uses Thereof – Delivery platform for targeted therapeutics, as well as uses thereof, including for delivery of any effector to the skin
+Added: 12/28/2036 Krystal
+Added: NZ 783621 New Zealand Composition of Matter & Uses Thereof – Delivery platform for targeted therapeutics, as well as uses thereof, including for delivery of any effector to the skin
+Added: 12/28/2036 Krystal
VYJUVEK / B-VEC
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12/28/2036 Krystal
−Removed: CL 69.593 Chile Composition of Matter & Uses Thereof – Compositions comprising replication-defective HSV vectors encoding certain effectors, including the effector encoded in B-VEC, as well as uses thereof, including for providing prophylactic, palliative or therapeutic relief of a wound, disorder or disease of the skin
−Removed: 12/28/2036 Krystal
Patent Number Country / Region *
Patent Type Expiration Date **
+Added: CL 69.593 Chile Composition of Matter & Uses Thereof – Compositions comprising replication-defective HSV vectors encoding certain effectors, including the effector encoded in B-VEC, as well as uses thereof, including for providing prophylactic, palliative or therapeutic relief of a wound, disorder or disease of the skin
+Added: 12/28/2036 Krystal
+Added: CL 70.567 Chile Composition of Matter & Uses Thereof – Compositions comprising HSV vectors encoding certain effectors, including the effector encoded in B-VEC, as well as uses thereof, including for providing prophylactic, palliative or therapeutic relief of a wound, disorder or disease of the skin
+Added: 12/28/2036 Krystal
IN 498868 India Composition of Matter – Compositions comprising replication-defective HSV vectors encoding certain effectors, including the effector encoded in B-VEC
2 unchanged sentences
12/28/2036 Krystal
−Removed: NZ New Zealand Composition of Matter & Uses Thereof – Pharmaceutical compositions comprising B-VEC, as well as uses thereof, including for providing prophylactic, palliative or therapeutic relief of a wound, disorder or disease of the skin
+Added: New Zealand Composition of Matter & Uses Thereof – Pharmaceutical compositions comprising B-VEC, as well as uses thereof, including for providing prophylactic, palliative or therapeutic relief of a wound, disorder or disease of the skin
12/28/2036 Krystal
3 unchanged sentences
Patent Type Expiration Date **
−Removed: 10,829,529 United States Methods of Use – Methods of using KB407 for the treatment of cystic fibrosis and other disease causing progressive lung destruction
+Added: 10,829,529 United States Methods of Use – Methods of using herpes virus vectors encoding CFTR for the treatment of cystic fibrosis and other disease causing progressive lung destruction
2/7/2040 Krystal
−Removed: ZA 2022/05420 South Africa Methods of Use – Methods of using KB407 for the treatment of cystic fibrosis and other disease causing progressive lung destruction
+Added: 12,522,636 United States Composition of Matter – Pharmaceutical compositions comprising replication-defective HSV-1 vectors encoding CFTR
2/7/2040 Krystal
+Added: AU 2020219343 Australia Composition of Matter & Uses Thereo f – Pharmaceutical compositions comprising herpes virus vectors encoding CFTR, as well as uses thereof, including for the treatment of cystic fibrosis and other disease causing progressive lung destruction
+Added: 2/7/2040 Krystal
+Added: CO 44406 Colombia Composition of Matter – Pharmaceutical compositions comprising replication-defective HSV-1 vectors encoding CFTR
+Added: 2/7/2040 Krystal
+Added: NZ 778665 New Zealand Composition of Matter & Uses Thereof – Pharmaceutical compositions comprising herpes virus vectors encoding CFTR, as well as uses thereof, including for the treatment of cystic fibrosis and other disease causing progressive lung destruction
+Added: 2/7/2040 Krystal
+Added: ZA 2022/05420 South Africa Methods of Use – Methods of using herpes virus vectors encoding CFTR for the treatment of cystic fibrosis and other disease causing progressive lung destruction
+Added: 2/7/2040 Krystal
Patent Number Country / Region *
Patent Type Expiration Date **
+Added: JP 7,773,468 Japan Composition of Matter & Uses Thereof – Pharmaceutical compositions comprising HSV vectors encoding certain effectors, including the effector encoded in KB408, and methods of using the same for treating a disease affecting the airways and/or lungs
+Added: 51488 Krystal
+Added: Patent Number Country / Region *
+Added: Patent Type Expiration Date **
11,779,660 United States Composition of Matter – Pharmaceutical compositions comprising HSV vectors encoding IL-2 and IL-12
2 unchanged sentences
4/14/2042 Krystal
+Added: 12,364,775 United States Methods of Use - Methods of use of HSV vectors encoding IL-2 and IL-12 for providing therapeutic relief of one or more signs or symptoms of lung cancer
+Added: 4/1/2042 Krystal
+Added: ZA 2025/02822 South Africa Composition of Matter – Pharmaceutical compositions comprising HSV vectors encoding IL-2 and IL-12
+Added: 4/1/2042 Krystal
+Added: ZA 2025/02821 South Africa Composition of Matter – Pharmaceutical compositions comprising HSV-1 vectors encoding IL-2 and IL-12
+Added: 4/1/2042 Krystal
Patent Number Country / Region *
2 unchanged sentences
4/11/2039 Krystal
−Removed: Patent Number Country / Region *
−Removed: Patent Type Expiration Date **
11,717,547 United States C omposition of Matter & Methods of Use – Pharmaceutical compositions comprising replication-defective HSV-1 vectors encoding TGM, as well as methods of delivering TGM to cells
4 unchanged sentences
4/11/2039 Krystal
−Removed: Other Dermatology
−Removed: Patent Number Country / Region *
−Removed: Patent Type Expiration Date **
11,642,384 United States Composition of Matter – Pharmaceutical compositions comprising eplication-defective HSV vectors encoding SPINK5
8 unchanged sentences
Patent Type Expiration Date **
+Added: JP 7,749,055 Japan Composition of Matter & Uses Thereof – Pharmaceutical compositions comprising replication-defective HSV vectors encoding one or more antibodies, and methods of using the same for treating a disease
+Added: 6/28/2039 Krystal
+Added: Patent Number Country / Region *
+Added: Patent Type Expiration Date **
10,786,438 United States C omposition of Matter & Methods of Use – Pharmaceutical compositions comprising HSV vectors encoding one or more cosmetic proteins, as well as methods of their use for improving skin condition, quality, and/or appearance
6 unchanged sentences
4/26/2039 Krystal
+Added: NZ 769822 New Zealand Composition of Matter –Compositions comprising HSV vectors encoding one or more cosmetic proteins
+Added: 4/26/2039 Krystal
ZA 2023/06237 South Africa
1 unchanged sentence
4/26/2039 Krystal
+Added: ZA 2025/01799 South Africa Composition of Matter & Uses thereof – Pharmaceutical compositions comprising HSV vectors encoding one or more cosmetic proteins, as well as uses thereof, including for improving skin condition, quality, and/or appearance
+Added: 4/26/2039 Krystal
* Granted patents in the U.S.
12 unchanged sentences
The FDCA, PHSA and their corresponding regulations govern, among other things, the testing, manufacturing, safety, efficacy, labeling, packaging, storage, record keeping, distribution, reporting, importation, advertising and other promotional practices involving biologic products.
−Removed: IND applications to the FDA are required before conducting human clinical
−Removed: testing of biologic products.
+Added: Investigational new drug, or IND, applications to the FDA are required before conducting human clinical testing of biologic products.
Additionally, each clinical trial protocol for a gene therapy product candidate is reviewed by the FDA, and in limited instances the National Institutes of Health (the “NIH”), through its Recombinant DNA Advisory Committee, or RAC.
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• completion of preclinical laboratory tests and in vivo studies in accordance with the FDA’s Current Good Laboratory Practice (“CGLP”), regulations and applicable requirements for the humane use of laboratory animals or other applicable regulations;
−Removed: • submission to the FDA of an IND application, which allows human clinical trials to begin unless FDA objects within 30 days;
+Added: • submission to the FDA of an IND application, which allows human clinical trials to begin unless the FDA objects within 30 days;
• approval by each clinical trial site’s Institutional Review Board (“IRB”) and, if applicable, Institutional Biosafety Committee (“IBC”), before the clinical trial may be initiated;
2 unchanged sentences
• review of the product by an FDA advisory committee, if applicable;
−Removed: • satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the biologic product candidate is produced to assess compliance with Current Good Manufacturing Practice (“CGMP”) requirements and to assure that the facilities, methods and controls are adequate to preserve the biologic product candidate’s identity, safety, strength, quality, potency and purity;
+Added: • satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the biologic product candidate is produced to assess compliance with CGMP requirements and to assure that the facilities, methods and controls are adequate to preserve the biologic product candidate’s identity, safety, strength, quality, potency and purity;
• potential FDA audit of the nonclinical and clinical trial sites that generated the data in support of the application;
60 unchanged sentences
The FDA reviews the BLA to determine, among other things, whether the proposed product candidate is safe and potent, or effective, for its intended use, has an acceptable purity profile and whether the product candidate is being manufactured in accordance with CGMP to assure and preserve the product candidate’s identity, safety, strength, quality, potency and purity.
−Removed: The FDA may refer applications for novel biologic products or biologic products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.
+Added: The FDA may refer applications for novel biologic products or biologic products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians
+Added: and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.
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Under the Orphan Drug Act, the FDA may designate a biologic product as an “orphan drug” if it is intended to treat a rare disease or condition, generally meaning that it affects fewer than 200,000 individuals in the United States, or more in cases in which there is no reasonable expectation that the cost of developing and making a biologic product available in the United States for treatment of the disease or condition will be recovered from sales of the product.
−Removed: If a product with orphan status receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, meaning that the FDA may not approve any other applications to market the same drug or biologic product for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity or if the party holding the exclusivity fails to assure the availability of sufficient quantities of the drug to meet the needs of patients with the disease or condition for which the drug was designated.
+Added: If a product with orphan status receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, meaning that the FDA may not approve any other applications to market the same drug or biologic product for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity or if the party holding the exclusivity fails to assure the availability of sufficient quantities of the drug to meet the needs of patients with the disease or condition for which the drug was
Competitors, however, may receive approval of different products for the same indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity.
41 unchanged sentences
Once the CTA request is approved in accordance with the EU and the EU Member State’s requirements, clinical trial development may proceed.
−Removed: The requirements and processes governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country.
−Removed: In all cases, the clinical trials are conducted in accordance with CGCPs and the applicable regulatory requirements of the country or countries in which the clinical trial is performed, as well as the ethical
−Removed: principles that have their origin in the Declaration of Helsinki (whichever provides the greater protection to the clinical trial participants).
+Added: The requirements and processes governing the conduct of clinical trials, product licensing, pricing and reimbursement in the EU vary from country to country.
+Added: In all cases, the clinical trials are conducted in accordance with the applicable EU laws and regulatory requirements of the country or countries in which the clinical trial is performed, as well as the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use’s guidelines on good clinical practice and ethical principles that have their origin in the Declaration of Helsinki (whichever provides the greater protection to the clinical trial participants).
Failure to comply with applicable foreign regulatory requirements may result in, among other things, fines;
17 unchanged sentences
• the federal Health Care Fraud statute imposes criminal and civil liability for executing, or attempting to execute, a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;
−Removed: • the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), and its implementing regulations, and as amended again by the final HIPAA omnibus rule (together with HIPAA and HITECH, the “HIPAA Rules”) which imposes privacy, security, and breach obligations, including mandatory contractual terms, with respect to safeguarding the security and privacy of individually identifiable health information by certain entities subject to the HIPAA Rules, such as health plans, health care clearinghouses, and health care providers that engage in certain covered transactions;
+Added: • the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), and its implementing regulations, and as amended again by the final HIPAA omnibus rule (together with HIPAA and HITECH, the “HIPAA
+Added: Rules”) which imposes privacy, security, and breach obligations, including mandatory contractual terms, with respect to safeguarding the security and privacy of individually identifiable health information by entities subject to the HIPAA Rules, such as health plans, health care clearinghouses, and health care providers that engage in certain covered transactions, as well as their business associates;
• the federal false statements statute prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for federally sponsored healthcare benefits, items or services;
2 unchanged sentences
state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures;
−Removed: and state and foreign laws governing the privacy and security of
−Removed: personal information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
+Added: and state and foreign laws governing the privacy and data security of personal information and health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
Violation of the laws described above or any other governmental laws and regulations may result in penalties, including civil and criminal penalties, damages, fines, the curtailment or restructuring of operations, the exclusion from participation in federal and state healthcare programs, disgorgement, contractual damages, reputational harm, diminished profits and future earnings, and imprisonment.
12 unchanged sentences
Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.
−Removed: In the EU, pricing and reimbursement schemes vary widely from country to country.
−Removed: Some countries provide that products may be marketed only after a reimbursement price has been agreed.
−Removed: Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently available therapies.
−Removed: EU member states may approve a specific price for a product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market.
−Removed: Other member states allow companies to fix their own prices for products, but monitor and control company profits.
+Added: In the EU, pricing and reimbursement schemes vary widely from member state to member state.
+Added: While a product may usually be legally placed on the market in the EU once a marketing authorization has been obtained, meaningful market access in many EU member states depends on the completion of national pricing and reimbursement procedures.
+Added: Some member states may require the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently available therapies.
+Added: Other member states may approve a specific price for a product or may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market.
The downward pressure on health care costs has become intense.
5 unchanged sentences
There is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality or expanding access.
−Removed: In the United States, for example, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected and continues to face major uncertainty due to the status of major legislative initiatives surrounding healthcare reform.
+Added: In the United States, for example, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected and continues to face major uncertainty due to the status of proposed and enacted legislative initiatives surrounding healthcare reform.
On August 16, 2022, the Inflation Reduction Act (“IRA”) was signed into law.
−Removed: The IRA includes several provisions to lower prescription drug costs for people with Medicare and reduce drug spending by the federal government, including allowing Medicare to negotiate prices for certain prescription drugs, requiring drug manufacturers to pay a rebate to the federal government if prices for single-source drugs and biologicals covered under Medicare Part B and nearly all covered drugs under Part D increase faster than the rate of inflation (CPI-U), and limiting out of pocket spending for Medicare Part D enrollees.
+Added: The IRA includes several provisions to lower prescription drug costs for
+Added: people with Medicare and reduce drug spending by the federal government, including allowing Medicare to negotiate prices for certain prescription drugs, requiring drug manufacturers to pay a rebate to the federal government if prices for single-source drugs and biologicals covered under Medicare Part B and nearly all covered drugs under Part D increase faster than the rate of inflation (CPI-U), and limiting out of pocket spending for Medicare Part D enrollees.
Additional Regulation
5 unchanged sentences
The United States Foreign Corrupt Practices Act (“FCPA”) prohibits United States corporations and individuals from engaging in certain activities to obtain or retain business abroad or to influence a person working in an official capacity.
−Removed: illegal to pay, offer to pay or authorize the payment of anything of value to any foreign government official, government staff member, political party or political candidate in an attempt to obtain or retain business or to otherwise influence a person working in an official capacity.
+Added: It is illegal to pay, offer to pay or authorize the payment of anything of value to any foreign government official, government staff member, political party or political candidate in an attempt to obtain or retain business or to otherwise influence a person working in an official capacity.
The scope of the FCPA includes interactions with certain healthcare professionals in many countries.
1 unchanged sentence
Human Capital
−Removed: As of February 12, 2025, we had 275 full-time employees, primarily engaged in research and development, pre-clinical and clinical trials, manufacturing VYJUVEK and our pipeline product candidates, commercial activities for VYJUVEK in the United States and commercialization preparations for VYJUVEK in the European Union and Japan, regulatory matters, strategic business development, finance and other technical matters, supply chain, and general and administrative services.
+Added: As of February 11, 2026, we had 295 full-time employees, primarily engaged in research and development, pre-clinical and clinical trials, manufacturing VYJUVEK and our pipeline product candidates, commercial activities for VYJUVEK in the United States, the European Union, and Japan, regulatory matters, strategic business development, finance and other technical matters, supply chain, and general and administrative services.
None of our employees are represented by a labor union and we consider our employee relations to be good.
9 unchanged sentences
In April 2019, we incorporated Jeune Aesthetics, Inc., a Delaware corporation and wholly-owned subsidiary, for the purpose of undertaking preclinical and clinical studies for aesthetic skin conditions.
−Removed: In January 2022, August 2022, December 2022, August 2023, March 2024, November 2024, and December 2024 we incorporated wholly-owned subsidiaries in Switzerland, Netherlands, France, Germany, Japan, Italy, and Spain respectively, for the purpose of establishing initial operations in Europe and Japan for the commercialization of VYJUVEK and our product pipeline.
+Added: In January 2022, August 2022, December 2022, August 2023, March 2024, November 2024, December 2024 and July 2025 we incorporated wholly-owned subsidiaries in Switzerland, Netherlands, France, Germany, Japan, Italy, Spain, and the UK, respectively, for the purpose of establishing operations in Europe and Japan for the commercialization of VYJUVEK ® and our product pipeline.
Our website address is www.krystalbio.com.
−Removed: Our website and the information contained on, or that can be accessed through, the website will not be deemed to be incorporated by reference in, and are not considered part of, this Annual Report on Form 10-K.
−Removed: You should not rely on any such information in making your decision whether to purchase our common stock.
−Removed: Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Exchange Act are available free of charge on the investor relations section of our website as soon as reasonably practicable after we electronically file such material with, or furnish it to the Securities and Exchange Commission, or the SEC.
+Added: Our website and the information contained on, or that can be accessed through, the website are not incorporated by reference in, and are not considered part of, this Annual Report on Form 10-K.
+Added: Access to our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and our Proxy Statements, and amendments to these reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Exchange Act are available free of charge on the investor relations section of our website as soon as reasonably practicable after we electronically file such material with, or furnish it to the Securities and Exchange Commission, or the SEC.
The SEC also maintains a website that contains reports, proxy and information statements, and other information regarding the Company that we file electronically with the SEC.
The address of the website is http://www.sec.gov.
+Added: We may use our website as a means of disclosing material non-public information and for complying with our disclosure obligations under the Regulation FD.
+Added: Accordingly, investors should monitor the investor relations section of our website, in addition to following the company’s press releases, SEC filings, public conference calls and webcasts, and our social media accounts.
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.