A Phase I Study of Inhaled KB407, a Replication-Incompetent, Non-Integrating Vector Expressing Human Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), for the Treatment of Cystic Fibrosis
The Sponsor is developing KB407, a replication-defective, non-integrating herpes simplex virus type 1 (HSV-1)-derived vector engineered to deliver functional full-length human Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) to the airways of people with cystic fibrosis via nebulization. This study is designed to evaluate safety and tolerability of KB407 in people with cystic fibrosis. This study will enroll 4 participants into each of the first two cohorts and will enroll five subjects into the last cohort. Cohort 1 will receive a single dose of KB407 and be followed for 60 days. Subjects in Cohort 1 may rollover into Cohort 2 at the Day 28 Visit. A Data Safety Monitoring Board (DSMB) will meet to determine study progress from Cohort 2 into Cohort 3. In Cohort 2, subjects will be dosed bi-weekly at Day 0 and Day 14. In Cohort 3 subjects will be dosed weekly at Day 0, Day 7, Day 14 and Day 21. All subjects will be followed for a year after the last dose of KB407.
• VYJUVEK™ approved in the U.S. as the first and only topical redosable gene therapy for the treatment of dystrophic epidermolysis bullosa • 121 Patient Start Forms in the first six weeks of launch • First cystic fibrosis patient dosed in Phase 1 Clinical Trial of KB407 • IND for KB707, Krystal’s first oncology candidate for solid tumors, accepted by FDA and granted Fast Track Designation • Strong balance sheet, closing the quarter with $505.9 million in cash, cash equivalents and investments PITTSBURGH, Aug. 07, 2023 (GLOBE NEWSWIRE) -- Krystal Biotech, Inc. (the “Company”) (NASDAQ: KRYS), a commercial-stage biotechnology company focused on the discovery, development and commercialization of genetic medicines to treat diseases with high unmet medical needs, today reported financial results and key operational progress updates for the second quarter ended June 30, 2023. “2023 is off to a very strong start and we expect the momentum to continue for the rest of the year. In the first half of the year, we received FDA approval for VYJUVEK, dosed our first patient in the cystic fibrosis trial and obtained IND clearance for our first oncology candidate,” said Krish S. Krishnan, Chairman and CEO of Krystal Biotech. “I am particularly thrilled with the enthusiasm that physicians and patients are expressing for VYJUVEK in these early days of launch. With 121 Patient Start Forms in the first six weeks since approval, I am pleased with the initial pace of the launch, and we look forward to promptly initiating treatment for these patients.” VYJUVEKTM On May 19, the Company announced that VYJUVEK (beremagene geperpavec-svdt, or B-VEC) was approved by the U.S. Food & Drug Administration (FDA) for the treatment of patients six months of age or older with either recessive or dominant dystrophic epidermolysis bullosa (DEB) to be administered by a healthcare professional either in a healthcare professional setting (e.g., clinic) or a home setting.As of June 30, the Company received 121 Patient Start Forms of which 30 start forms were generated for patients with dominant dystrophic epidermolysis bullosa. The Company will continue to report on the number of Patient Start Forms submitted to the Company for the first three quarters following VYJUVEK approval and will transition to reporting on the number of Patients on Therapy beginning in the first quarter of 2024.The Company also received positive coverage determinations from several of the national health plans, including UnitedHealthcare, as well as regional plans such as BlueCross BlueShield, state Medicaid plans and other smaller regional health plans. The Company expects that additional payer policies will continue to publish that cover VYJUVEK for both recessive and dominant DEB patients.In July, the Company received a positive opinion from the European Medical Agency (EMA) on the Pediatric Investigation Plan for B-VEC for the treatment of DEB with no additional studies required. The Company plans to submit a market authorization application to the EMA in the second half of 2023 and anticipates a potential launch in the EU in the second half of 2024.In July, the Pharmaceuticals and Medical Agency in Japan accepted the open label extension study of B-VEC, and the Company intends to start an open label extension study of B-VEC in Japan in the second half of 2023 and file for approval in Japan in 2024. The Company will provide details of the open label extension study when it doses the first patient in Japan. Respiratory KB407 for the treatment of Cystic Fibrosis (CF) In July, the Company announced that the first patient had been dosed at the Cystic Fibrosis Institute of Chicago in the Company’s Phase 1 CORAL-1/U.S. study evaluating KB407, a mutation agnostic genetic medicine, delivered via a nebulizer, for the treatment of patients with CF. The Phase 1/CORAL-1 study is a multi-center, dose-escalation trial of KB407 in patients with CF, regardless of their underlying genotype. The Company anticipates announcing data from the Phase 1 study in 2024. Details of the Phase 1 study can be found at www.clinicaltrials.gov under NCT identifier NCT05504837. KB408 for the treatment of Alpha-1 Antitrypsin Deficiency (AATD) The Company intends to file an Investigational New Drug (IND) application with the FDA and initiate a Phase 1 clinical trial of KB408 for the treatment of AATD in the second half of 2023. Oncology KB707 for the treatment of solid tumors In July, the Company announced that the FDA had accepted its IND application to evaluate intratumoral KB707 in a clinical trial to treat patients with locally advanced or metastatic solid tumor malignancies. KB707 targets solid tumors that are accessible via intratumoral injection or inhalation, and we intend to advance both routes of administration into clinical studies. Details of the Phase 1 (OPAL-1) study can be found www.clinicaltrials.gov under NCT identifier NCT05970497. The Company expects to dose the first patient in the second half of 2023.The FDA also granted KB707 fast track designation to delay disease progression in the treatment of patients with anti-PD-1 relapsed/refractory locally advanced or metastatic melanoma.The Company plans to file an amendment to the existing KB707 IND in the second half of 2023 to allow the Company to evaluate inhaled (nebulized) KB707 in a clinical trial to treat tumors in a patient’s lungs. The Company expects to dose the first patient with inhaled KB707 in the first half of 2024. Dermatology KB105 for the treatment of TGM1 deficient autosomal recessive congenital ichthyosis The Company plans to initiate the Phase 2 cohort of its KB105-02 (JADE-1) trial in 2024 and is currently working with the FDA to ensure alignment on the clinical endpoints in the pivotal trial prior to initiating a Phase 2 study in pediatric patients. The Phase 2 cohort will enroll both pediatric and adult patients with TGM1 deficient autosomal recessive congenital ichthyosis for assessment of KB105 safety and efficacy. Details of the Phase 1/2 study can be found at www.clinicaltrials.gov under NCT identifier NCT04047732. KB104 for the treatment of Netherton Syndrome With an expanding pipeline portfolio, the Company now anticipates filing an IND application with the FDA and initiating a clinical trial of KB104 to treat patients with Netherton Syndrome in late 2024. Aesthetics KB301 for the treatment of aesthetic indications In April, Jeune Aesthetics, Inc., a wholly-owned subsidiary of the Company, announced the dosing of the first subject in the Phase 1, Cohort 3 study of KB301 for the improvement of lateral canthal lines at rest. The study is on-going, and the Company plans to announce results from this study in the second half of 2023. Details of the Phase 1 study can be found at www.clinicaltrials.gov under NCT identifier NCT04540900. Financial results for the quarter ended June 30, 2023: Cash, cash equivalents, and investments totaled $505.9 million on June 30, 2023.Research and development expenses for the quarter ended June 30, 2023 were $12.1 million, inclusive of $2.9 million of stock-based compensation, compared to $10.9 million, inclusive of stock-based compensation of $2.0 million for the quarter ended June 30, 2022.General and administrative expenses for the quarter ended June 30, 2023 were $25.9 million, inclusive of stock-based compensation of $8.5 million, compared to $17.9 million, inclusive of stock-based compensation of $6.2 million, for the quarter ended June 30, 2022.Net losses for the quarters ended June 30, 2023 and 2022 were $33.2 million and $28.1 million, or $(1.25) and $(1.10), respectively, per common share (basic and diluted).For additional information on the Company’s financial results for the quarter ended June 30, 2023, please refer to the Form 10-Q filed with the SEC. Financial results for the six months ended June 30, 2023: Research and development expenses for the six months ended June 30, 2023 were $24.4 million, inclusive of stock-based compensation of $5.4 million, compared to $20.2 million, inclusive of stock-based compensation of $3.4 million for the six months ended June 30, 2022.General and administrative expenses for the six months ended June 30, 2023 were $49.9 million, inclusive of stock-based compensation of $16.4 million, compared to $33.8 million, inclusive of stock-based compensation of $11.3 million for the six months ended June 30, 2022.Net losses for the six months ended June 30, 2023 and 2022 were $78.5 million and $78.1 million or $(3.00) and $(3.08), respectively, per common share (basic and diluted).For additional information on the Company’s financial results for the six months ended June 30, 2023, please refer to the Form 10-Q filed with the SEC. About VYJUVEK VYJUVEK is a non-invasive, topical, redosable gene therapy designed to deliver two copies of the COL7A1 gene when applied directly to DEB wounds. VYJUVEK was designed to treat 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. Indication VYJUVEK is a herpes-simplex virus type 1 (HSV-1) vector-based gene therapy indicated for the treatment of wounds in patients six months of age and older with dystrophic epidermolysis bullosa with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene. IMPORTANT SAFETY INFORMATION Adverse Reactions The most common adverse drug reactions (incidence >5%) were itching, chills, redness, rash, cough, and runny nose. These are not all the possible side effects with VYJUVEK. Call your healthcare provider for medical advice about side effects. To report SUSPECTED ADVERSE REACTIONS, contact Krystal Biotech, Inc. at 1-844-557-9782 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. Contraindications None. Warnings and Precautions VYJUVEK gel must be applied by a healthcare provider. After treatment, patients and caregivers should be careful not to touch treated wounds and dressings for 24 hours. Wash hands and wear protective gloves when changing wound dressings. Disinfect bandages from the first dressing change with a virucidal agent, and dispose of the disinfected bandages in a separate sealed plastic bag in household waste. Dispose of the subsequent used dressings in a sealed plastic bag in household waste. Patients should avoid touching or scratching wound sites or wound dressings. In the event of an accidental exposure flush with clean water for at least 15 minutes. For more information, see full U.S. Prescribing Information. About Fast Track Designation Fast Track Designation is designed to facilitate the development and expedite the review of drugs to treat serious conditions and treat a serious or unmet medical need, enabling drugs to reach patients sooner. Clinical programs with Fast Track designation may benefit from early and frequent communication with the FDA throughout the regulatory review process, and such clinical programs may be eligible to apply for Accelerated Approval and Priority Review if relevant criteria are met. About Krystal Biotech, Inc. Krystal Biotech, Inc. (NASDAQ: KRYS) is a commercial-stage biotechnology company focused on the discovery, development and commercialization of genetic medicines to treat diseases with high unmet medical needs. VYJUVEKTM is the Company’s first commercial product, the first-ever redosable gene therapy, and the only medicine approved by the FDA for the treatment of dystrophic epidermolysis bullosa. The Company is rapidly advancing a robust preclinical and clinical pipeline of investigational genetic medicines in respiratory, oncology, dermatology, ophthalmology, and aesthetics. Krystal Biotech is headquartered in Pittsburgh, Pennsylvania. For more information, please visit http://www.krystalbio.com, and follow @KrystalBiotech on LinkedIn and Twitter. About Jeune Aesthetics, Inc. Jeune Aesthetics, Inc., a wholly-owned subsidiary of Krystal Biotech, Inc., is a biotechnology company leveraging a clinically validated gene-delivery platform to develop products to fundamentally address – and reverse – the biology of aging and/or damaged skin. For more information, please visit http://www.jeuneinc.com. Forward-Looking Statements Any statements in this press release about future expectations, plans and prospects for Krystal Biotech, Inc. or Jeune Aesthetics, Inc., including statements about our commercial launch of VYJUVEK; our plans to report on Patient Start Forms and Patients on Therapy; our plans to submit a market authorization application to the EMA in the second half of 2023 and our anticipation of a potential launch of B-VEC in the EU in the second half of 2024; our plans for an open label extension study of B-VEC in Japan in the second half of 2023, filing for approval in Japan in 2024, and the timing of our provision of details of the open label extension study; our expectation that we will announce data from the Phase 1 study of KB407 in 2024; our intention to file an IND application with the FDA and initiate a Phase 1 clinical trial of KB408 for the treatment of AATD in the second half of 2023; our expectations regarding dosing the first patient with KB707 in the second half of 2023; our plans to file an amendment to the existing KB707 IND in the second half of 2023 to evaluate inhaled KB707 in a clinical trial in the first half 2024; our plans to initiate the Phase 2 cohort of the KB105-02 (JADE-1) trial in 2024; our plans to file an IND application and initiate a clinical trial of KB104 in late 2024; our expectation that we will announce results of the Phase 1, Cohort 3 study of KB301 for the improvement of lateral canthal lines at rest in the second half of 2023, and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “likely,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties associated with regulatory review of clinical trials and applications for marketing approvals, the availability or commercial potential of product candidates including VYJUVEK, the sufficiency of cash resources and need for additional financing and such other important factors as are set forth under the caption “Risk Factors” in the Company’s annual and quarterly reports on file with the U.S. Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date of this release. The Company anticipates that subsequent events and developments will cause its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this release. Disclosures The Company is using the Aerogen Solo® Nebulizer System and Aerogen® Ultra in its Phase 1 CORAL-1/U.S. study evaluating KB407. CONTACT:Investors and Media:Meg DodgeKrystal Biotechmdodge@krystalbio.com Consolidated Balance Sheet Data: (In thousands)June 30,2023 December 31,2022 Balance sheet data: Cash and cash equivalents$275,875 $161,900 Short-term investments 201,642 217,271 Long-term investments 28,410 4,621 Total assets 684,026 558,450 Total liabilities 30,912 36,219 Total stockholders’ equity$653,114 $522,231 Consolidated Statements of Operations: Three Months EndedJune 30, (In thousands, except shares and per share data) 2023 2022 ChangeExpenses
Research and development$12,144 $10,890 $1,254 General and administrative 25,904 17,863 8,041 Total operating expenses 38,048 28,753 9,295 Loss from operations (38,048) (28,753) (9,295)Other Income
Interest and other income, net 4,838 645 4,193 Net loss$(33,210) $(28,108) $(5,102)
Net loss per common share: Basic and diluted$(1.25) $(1.10)
Weighted-average common shares outstanding: Basic and diluted 26,656,883 25,545,167
Six Months Ended June 30, 2023 2022 Change(In thousands)(unaudited) Expenses
Research and development$24,432 $20,204 $4,228 General and administrative 49,939 33,771 16,168 Litigation settlement 12,500 25,000 (12,500)Total operating expenses 86,871 78,975 7,896 Loss from operations (86,871) (78,975) (7,896)Other Income
Interest and other income, net 8,364 902 7,462 Net loss$(78,507) $(78,073) $(434)
Net loss per common share: Basic and diluted$(3.00) $(3.08)
Weighted-average common shares outstanding: Basic and diluted 26,187,161 25,331,000
Krystal Biotech, Inc. (the “Company”) (NASDAQ: KRYS), a biotechnology company focused on developing and commercializing genetic medicines for patients with debilitating diseases, announced today that the first patient has been dosed at the Cystic Fibrosis Institute of Chicago in the Company’s Phase 1 CORAL-1/US study evaluating KB407, an engineered HSV-1-based, aerosol-delivered, mutation agnostic, genetic medicine for the treatment of patients with cystic fibrosis (CF).
“By delivering full-length copies of CFTR directly to the lung via nebulization, KB407 has the potential to address the basic genetic defect present in cystic fibrosis,” said Steven R. Boas, M.D., Director of the Cystic Fibrosis Institute and Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “As this therapy does not depend on the type of CFTR mutation present, KB407 may potentially benefit all individuals affected by cystic fibrosis.”
“Dosing our first patient in the KB407 Phase 1 clinical trial is an exciting step forward for the company and for the patients we aim to benefit,” said Hubert Chen, M.D., Senior Vice President of Clinical Development at Krystal Biotech. “Not only is the Phase 1 study designed to provide key insights into the safety and efficacy of KB407, it is also a critical step in expanding our vector platform to tissues beyond the skin. We look forward to continued enrollment into the Phase 1 study with anticipated data in 2024.”
CORAL-1/US Study Overview
The CORAL-1/US study is a multicenter, dose-escalation trial of KB407 in patients (n~20) with CF regardless of their underlying genotype. Each administration of KB407 will be nebulized in under 30 minutes. This study will include three cohorts and enroll five subjects each in the first two cohorts and ten subjects in the last cohort.
Cohort 1 participants will receive a single administration of KB407 on Day 0, and Cohort 2 participants will receive administrations of KB407 on Day 0 and Day 1. Cohorts 1 and 2 will be conducted on an open-label basis and up to 3 subjects in each of the first two cohorts may receive concurrent CFTR modulator therapy. Cohort 3 participants will be randomized 4:1 to receive administrations of KB407 or placebo on Day 0, Day 1, Day 2, and Day 3. Cohort 3 will follow a randomized, placebo-controlled, and double-blind design and will enroll only subjects who are not otherwise eligible for CFTR modulators. A Data Monitoring Committee will conduct a safety review after each cohort before proceeding to the next one.
The primary endpoint of the trial will be the safety and tolerability of nebulized KB407. Changes in lung function from baseline will be assessed by the percent predicted forced expiratory volume in one second (ppFEV1). Vector shedding and biodistribution will also be assessed in blood, urine, buccal, and sputum samples. The CORAL-1/US study also includes a bronchoscopy sub-study for assessment of CFTR transgene expression in the airways at both the nucleic acid and protein levels. At select sites, subjects may undergo an optional bronchoscopy 24 to 96 hours after the last dose of KB407. The bronchoscopy will include bronchial brushings and endobronchial biopsies.
Details about the Phase 1 study can be found at www.clinicaltrials.gov under NCT identifier NCT05504837.
KB407 is an investigational, redosable gene therapy designed to molecularly correct the underlying cause of CF by delivering two copies of the CFTR gene directly to the airways via nebulization. By enabling the expression of full-length, healthy CFTR protein in the lung, treatment with KB407 has the potential to restore proper anion transport within transduced cells to correct the lung manifestations of the disease. Because KB407 is engineered to enable expression of wild-type CFTR protein, treatment is agnostic to patients’ underlying CFTR mutations. The US Food and Drug Administration and the European Commission have granted orphan drug designation for KB407 to treat patients with CF.
About Cystic Fibrosis
CF is a genetic disease caused by mutations in the CFTR gene which result in dysfunctional or absent CFTR protein, and buildup of mucus in the lungs that leads to persistent lung infections and progressive pulmonary disease. The Cystic Fibrosis Foundation estimates that there are close to 40,000 children and adults living with CF in the US, and an estimated 105,000 people diagnosed with CF across 94 countries. People of every racial and ethnic group are affected by this debilitating disease.
Although CFTR modulators are effective in patients with certain CFTR mutations, patients may still experience pulmonary symptoms requiring treatment. Importantly, approximately 10-15% of CF patients harbor genetic mutations that are not expected to be responsive to approved therapies and currently have no available disease-modifying treatment options, representing a significant unmet need.
About Krystal Biotech, Inc.
Krystal Biotech, Inc. (NASDAQ: KRYS) is a commercial-stage fully integrated company focused on developing genetic medicines for patients with debilitating diseases. VYJUVEKTM is the Company’s first commercial product, the first-ever redosable gene therapy, and the only medicine approved by the FDA for the treatment of dystrophic epidermolysis bullosa. The Company presently has three candidates in clinical development and a wide-ranging pipeline that is powered by its proprietary, redosable HSV-1 gene delivery platform.
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