COL3A1

NEWTON, Mass., Aug. 30, 2023 (GLOBE NEWSWIRE) -- Acer Therapeutics Inc. (Nasdaq: ACER), a pharmaceutical company focused on the acquisition, development and commercialization of therapies for serious, rare and life-threatening diseases with significant unmet medical needs, today announced it has entered into definitive agreements to reacquire worldwide development, commercialization and economic rights to OLPRUVA™ (sodium phenylbutyrate) from Relief Therapeutics, excluding the European Union, Liechtenstein, San Marino, Vatican City, Norway, Iceland, Principality of Monaco, Andorra, Gibraltar, Switzerland, United Kingdom, Albania, Bosnia, Kosovo, Montenegro, Serbia and North Macedonia (Geographical Europe). OLPRUVA™ is approved in the U.S. for the treatment of certain urea cycle disorders (UCDs). Under the prior Collaboration and License Agreement (CLA) between the parties, Acer would have paid Relief 60% of Acer's OLPRUVA™ net profits in the U.S., Canada, Brazil, Turkey and Japan (the Acer territories), while Acer would have received a 15% royalty on Relief’s net sales in the rest of the world (the Relief territories). Acer and Relief have now agreed to terminate the CLA, where Acer is no longer required to pay Relief 60% of OLPRUVA™ net profits in the Acer territories and have regained all development and commercialization rights in rest of the world, excluding the Geographical Europe. In return, Relief will receive an upfront payment by Acer of $10 million, to be made within 5 business days of the signature date, with an additional payment of $1.5 million due on the first-year anniversary of the $10 million payment. Acer has also agreed to pay a 10% royalty on net sales in the Acer territories, and 20% of any value received by Acer from certain third parties relating to OLPRUVA™ licensing or divestment rights, all of the foregoing which are capped at $45 million, for total payments to Relief of up to $56.5 million. Additionally, Acer and Relief have entered into a new Exclusive License Agreement (ELA) in which Relief will retain development and commercialization rights for OLPRUVA™ in the Geographical Europe, where Acer will have the right to receive a royalty of up to 10% of the net sales of OLPRUVA™. “Regaining exclusive worldwide rights to OLPRUVA™ without profit sharing, subject only to Relief's rights in the Geographical Europe, unlocks value for Acer as we continue the U.S. launch of OLPRUVA™ and begin to provide treatments to UCD patients in need,” said Chris Schelling, CEO and Founder of Acer. “Reacquiring greater economic rights to OLPRUVA™ allows Acer to reinvest more capital into potential lifecycle expansion opportunities for OLPRUVA™, in additional inborn errors of metabolism, such as Maple Syrup Urine Disease and other potential indications.” “We are very happy to have restructured our collaboration with Acer Therapeutics which we believe will benefit those suffering from UCDs and other potential rare metabolic conditions,” said Jack Weinstein, CEO of Relief Therapeutics. “Our collective goal with Acer is to maximize the global commercialization of OLPRUVA™ to ensure as many patients as possible will access this much needed, differentiated and convenient alternative.” Additional information regarding the termination of the March 2021 CLA and execution of the new ELA for European rights is available on form 8-K at . OLPRUVA™: Now Available by Prescription in U.S. ACER-001 (sodium phenylbutyrate) was approved for the treatment of certain UCDs in December 2022 and is marketed under the brand name, OLPRUVA™. OLPRUVA™ (sodium phenylbutyrate) for oral suspension is a prescription medicine used along with certain therapy, including changes in diet, for the long-term management of adults and children weighing 44 pounds (20 kg) or greater and with a BSA of 1.2 m2 or greater, with UCDs, involving deficiencies of CPS, OTC, or AS.1 Please see full Prescribing Information, including Patient Information. Important Safety Information Certain medicines may increase the level of ammonia in the blood or cause serious side effects when taken during treatment with OLPRUVA™. Tell your doctor about all the medicines you or your child takes, especially if you or your child takes corticosteroids, valproic acid, haloperidol, and/or probenecid. OLPRUVA™ can cause serious side effects, including: 1) nervous system problems (neurotoxicity) such as, sleepiness, tiredness, lightheadedness, vomiting, nausea, headache, and/or confusion, 2) low potassium levels in your blood (hypokalemia) and 3) conditions related to swelling (edema). OLPRUVA™ contains salt (sodium), which can cause swelling from salt and water retention. Tell your doctor right away if you or your child get any of these symptoms. Your doctor may do certain blood tests to check for side effects during treatment with OLPRUVA. If you have certain medical conditions such as heart, liver or kidney problems, are pregnant/planning to get pregnant or breast-feeding, your doctor will decide if OLPRUVA™ is right for you. The most common side effects of OLPRUVA™ include absent or irregular menstrual periods, decreased appetite, body odor, bad taste or avoiding foods you ate prior to getting sick (taste aversion). These are not all of the possible side effects of OLPRUVA™. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For additional Important Safety Information, see full Prescribing Information, Patient Package Insert and discuss with your doctor. About Acer Therapeutics Acer is a pharmaceutical company focused on the acquisition, development and commercialization of therapies for serious rare and life-threatening diseases with significant unmet medical needs. In the U.S., OLPRUVA™ (sodium phenylbutyrate) is approved for the treatment of UCDs involving deficiencies of CPS, OTC, or AS. Acer is also advancing a pipeline of investigational product candidates for rare and life-threatening diseases, including: OLPRUVA™ (sodium phenylbutyrate) for treatment of various disorders, including Maple Syrup Urine Disease (MSUD); and EDSIVO™ (celiprolol) for treatment of vascular Ehlers-Danlos syndrome (vEDS) in patients with a confirmed type III collagen (COL3A1) mutation. For more information, visit . References OLPRUVA™ (sodium phenylbutyrate) for oral suspension. Prescribing information. Newton, MA: Acer Therapeutics Inc. Acer Forward-Looking Statements This press release contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this press release are forward-looking statements. Examples of such statements include, but are not limited to, expected payments between Acer and Relief in connection with the ELA and terminated CLA, the impact of the revised business arrangement between Acer and Relief on the Company and the Company’s investment plans related thereto, plans with respect to the U.S. launch of OLPRUVA™, and the possible side effects of OLPRUVA™. Additionally, the Company’s effort to advance a pipeline of investigational product candidates and related plans and expectations is an example of such forward-looking statements. Our efforts to commercialize OLPRUVA™ for oral suspension in the U.S. for the treatment of certain patients with UCDs involving deficiencies of CPS, OTC, or AS are at an early stage, we currently do not have fully developed marketing and sales capabilities, and there is no guarantee that we will be successful in our commercialization efforts. Our pipeline products (including OLPRUVA™ for indications other than UCDs) are under investigation and their safety and efficacy have not been established and there is no guarantee that any of our investigational products in development will receive health authority approval or become commercially available for the uses being investigated. We may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements and you should not place undue reliance on these forward-looking statements. Such statements are based on management’s current expectations and involve risks and uncertainties. Actual results and performance could differ materially from those projected in the forward-looking statements as a result of many factors, including, without limitation, the availability of financing to fund our commercialization efforts, our pipeline product development programs and general corporate operations as well as risks related to drug development and the regulatory approval process, including the timing and requirements of regulatory actions. We disclaim any intent or obligation to update these forward-looking statements to reflect events or circumstances that exist after the date on which they were made. You should review additional disclosures we make in our filings with the Securities and Exchange Commission, including our Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. You may access these documents for no charge at . Corporate and IR Contacts Harry Palmin Chief Financial Officer Acer Therapeutics Inc. investors@acertx.com +1-844-902-6100 Nick Colangelo Gilmartin Group nick@gilmartinIR.com +1-332-895-3226

OLPRUVA™ (sodium phenylbutyrate) kits now available in all dosage strengths and ready to ship to patients NEWTON, Mass., Aug. 14, 2023 (GLOBE NEWSWIRE) -- Acer Therapeutics Inc. (Nasdaq: ACER), a pharmaceutical company focused on the acquisition, development and commercialization of therapies for serious, rare and life-threatening diseases with significant unmet medical needs, today reported financial results for the second quarter ended June 30, 2023 and provided a corporate update. “The second quarter of 2023 marked continued progress for Acer as we execute on our OLPRUVA™ launch strategy,” said Chris Schelling, CEO and Founder of Acer. “We are pleased to offer OLPRUVA™ in the U.S. to certain UCD patients as a novel alternative option to current treatments that was specifically designed for palatability and convenience.1,2 With OLPRUVA™ kits now available in all dosage strengths, we are committed to supporting patients from initial prescription to support throughout the treatment process and look forward to making OLPRUVA™ available to patients in need.” Program and Corporate Highlights OLPRUVA™ (sodium phenylbutyrate) for oral suspension OLPRUVA™ kits are now available in all dosage strengths and ready to ship to patients A dedicated OLPRUVA™ Navigator Team at CVS Specialty is now available to provide prescription fulfillment support throughout the treatment process; healthcare provider and patient resources are also now available at and Acer Therapeutics is in discussions with both commercial and government payers and is actively engaged with the major pharmacy benefits managers (PBM) and group purchasing organizations (GPO) representing a substantial majority of covered lives Corporate Ended Q2 2023 with $1.6 million in cash and cash equivalents. Acer believes its cash and cash equivalents available as of June 30, 2023 will be sufficient to fund its anticipated operating and capital requirements through mid-Q3 2023 Anticipated Milestones (Subject to Available Capital) Q3 2023: Acer expects to begin attaining OLPRUVA™ commercial insurance coverage in Q3 2023 Q3 2023: Acer expects to begin attaining insurance coverage for OLPRUVA™ Medicaid patients starting in Q3 2023 H1 2024: Acer anticipates enrollment completion in H1 2024 of its pivotal Phase 3 DiSCOVER trial of EDSIVO™ in patients with COL3A1-positive vEDS Acer also intends to pursue additional opportunities for potential OLPRUVA™ label expansion, including the potential for additional dosage strengths to address patients with lower weights/body surface areas, and potential administration using a gastrostomy tube (G-tube) Q2 2023 Financial Results Cash Position. Cash and cash equivalents were $1.6 million as of June 30, 2023, compared to $2.3 million as of December 31, 2022. Acer believes its cash and cash equivalents at June 30, 2023 will be sufficient to fund its anticipated operating and capital requirements through the middle of the third quarter of 2023. Research and Development Expenses. Research and development expenses were $1.4 million, net of collaboration funding of $0.6 million, for the three months ended June 30, 2023, as compared to $3.4 million, net of collaboration funding of $1.6 million, for the three months ended June 30, 2022. This decrease of $2.0 million was primarily due to decreases in expenses for clinical studies, employee-related expenses, expenses for consulting and professional services, and contract manufacturing expenses. Research and development expenses related to ACER-001 decreased in the three months ended June 30, 2023, resulting in a decrease in the recognition of the collaboration funding from the Collaboration Agreement with Relief. Research and development expenses for the three months ended June 30, 2023 were comprised of $1.0 million related to EDSIVOTM; $0.6 million related to ACER-001, offset by $0.6 million of collaboration funding; $0.2 million related to ACER-801; and $0.2 million related to other development activities. General and Administrative Expenses. General and administrative expenses were $2.9 million, net of collaboration funding of $1.4 million, for the three months ended June 30, 2023, as compared to $3.6 million, net of collaboration funding of $3.3 million, for the three months ended June 30, 2022. This decrease of $0.7 million was primarily due to decreases in marketing expenses, expenses for consulting and professional services, and employee-related expenses. General and administrative expenses related to ACER-001 decreased in the three months ended June 30, 2023, resulting in a decrease in the recognition of the collaboration funding from the Collaboration Agreement with Relief. Net Loss. Net loss for the three months ended June 30, 2023 was $8.1 million, or $0.33 net loss per share (basic and diluted), compared to a net loss of $2.7 million, or $0.17 net loss per share (basic and diluted), for the three months ended June 30, 2022. For additional information, please see Acer’s Quarterly Report on Form 10-Q filed today with the Securities and Exchange Commission (SEC). About Acer Therapeutics Acer is a pharmaceutical company focused on the acquisition, development and commercialization of therapies for serious rare and life-threatening diseases with significant unmet medical needs. In the U.S., OLPRUVA™ (sodium phenylbutyrate) is approved for the treatment of UCDs involving deficiencies of CPS, OTC, or AS. Acer is also advancing a pipeline of investigational product candidates for rare and life-threatening diseases, including: OLPRUVA™ (sodium phenylbutyrate) for treatment of various disorders, including Maple Syrup Urine Disease (MSUD); and EDSIVO™ (celiprolol) for treatment of vascular Ehlers-Danlos syndrome (vEDS) in patients with a confirmed type III collagen (COL3A1) mutation. For more information, visit . References OLPRUVA™ (sodium phenylbutyrate) for oral suspension. Prescribing information. Newton, MA: Acer Therapeutics Inc. Appel LE, Shockey JR, Schelling DC, inventors; Acer Therapeutics Inc, assignee. Palatable compositions including sodium phenylbutyrate and uses thereof. US patent 11,154,521 (B2). October 26, 2021. Acer Forward-Looking Statements This press release contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this press release are forward-looking statements. Examples of such statements include, but are not limited to, statements about plans and strategy for the commercialization of OLPRUVA™ for oral suspension in the U.S. for the treatment of certain patients with certain UCDs, including progress with respect to discussions with commercial and government insurance providers, physicians outreach and awareness, and patient support and fulfillment, statements with respect to our EDSIVO clinical trial for patients with vEDS, including enrollment and timing milestones related thereto, statements about our anticipated 2023 milestones, statements about our investment of OLPRUVA revenue, and statements about our capital requirements and sufficiency and duration of our current cash and cash equivalents. Our efforts to commercialize OLPRUVA™ for oral suspension in the U.S. for the treatment of certain patients with UCDs involving deficiencies of CPS, OTC, or AS are at an early stage, we currently do not have fully developed marketing, sales or distribution capabilities, and there is no guarantee that we will be successful in our commercialization efforts. Our pipeline products (including OLPRUVA™ for indications other than UCDs as well as EDSIVO™ and ACER-801) are under investigation and their safety and efficacy have not been established and there is no guarantee that any of our investigational products in development will receive health authority approval or become commercially available for the uses being investigated. We may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements and you should not place undue reliance on these forward-looking statements. Such statements are based on management’s current expectations and involve risks and uncertainties. Actual results and performance could differ materially from those projected in the forward-looking statements as a result of many factors, including, without limitation, the availability of financing to fund our commercialization efforts, our pipeline product development programs and our general corporate operations as well as risks related to drug development and the regulatory approval process, including the timing and requirements of regulatory actions. We disclaim any intent or obligation to update these forward-looking statements to reflect events or circumstances that exist after the date on which they were made. You should review additional disclosures we make in our filings with the Securities and Exchange Commission, including our Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. You may access these documents for no charge at ACER THERAPEUTICS INC. CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited) Three Months Ended June 30, 2023 2022 Operating expenses: Research and development (net of collaboration funding of $600,072 and $1,648,631 in the three months ended June 30, 2023 and 2022, respectively) $ 1,440,717 $ 3,426,773 General and administrative (net of collaboration funding of $1,404,695 and $3,257,701 in the three months ended June 30, 2023 and 2022, respectively) 2,853,760 3,638,073 Loss from operations (4,294,477 ) (7,064,846 ) Other income (expense), net: Costs of debt issuance — (200,129 ) Loss on extinguishment of debt (350,000 ) — Changes in fair value of debt instruments (loss) gain (2,806,538 ) 4,729,460 Interest and other income (expense), net (639,610 ) (139,234 ) Foreign currency transaction (loss) gain (95 ) 7,713 Total other income (expense), net (3,796,243 ) 4,397,810 Net loss $ (8,090,720 ) $ (2,667,036 ) Net loss per share - basic $ (0.33 ) $ (0.17 ) Weighted average common shares outstanding - basic 24,462,895 15,273,707 Net loss per share - diluted $ (0.33 ) $ (0.30 ) Weighted average common shares outstanding - diluted 24,462,895 17,681,400 SELECTED BALANCE SHEET DATA (Unaudited): June 30, December 31, 2023 2022 Cash and cash equivalents $ 1,553,416 $ 2,329,218 Inventory $ 4,600,618 $ — Prepaid expenses $ 583,339 $ 759,292 Deferred financing costs $ — $ 408,000 Other current assets $ 14,638 $ 20,188 Property and equipment, net $ 54,273 $ 214,578 Total assets $ 14,648,276 $ 11,624,226 Accounts payable and accrued expenses $ 10,438,490 $ 7,470,674 Promissory Note payable to an officer $ 1,000,000 $ — Deferred collaboration funding, total $ 4,547,198 $ 8,412,971 SWK Loans payable, at fair value $ 17,986,848 $ 5,567,231 Convertible note payable, at fair value $ 13,078,200 $ 6,047,532 Total liabilities $ 47,894,494 $ 28,385,498 Total stockholders’ deficit $ (33,246,218 ) $ (16,761,272 ) Corporate and IR Contact Jim DeNike Acer Therapeutics Inc. jdenike@acertx.com +1-844-902-6100 Nick Colangelo Gilmartin Group nick@gilmartinIR.com +1-332-895-3226

▲8月03-04日 CMC-China大会 · 限时免费扫码报名中注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。里程碑式基因疗法斩获多项“第一”药融圈旗下，药融云数据www.pharnexcloud.com显示：2023年5月19日，美国FDA批准了Krystal Biotech公司开发的基因疗法VYJUVEK™（beremagene geperpavec-svdt，B-VEC）凝胶用于治疗6月龄及以上营养不良型大疱性表皮松解症（DEB）患者。VYJUVEK™（B-VEC）是一款里程碑式疗法，斩获多项“第一”：是FDA批准的首款局部外用的涂抹型基因疗法、有史以来首个可重复使用的基因治疗药物，也是首个且目前唯一的针对DEB的基因治疗药物。该药物基于单纯疱疹病毒1型（HSV-1）开发，旨在通过递送人COL7A1基因的功能性拷贝，从根本上解决DEB的遗传病因，以促进伤口愈合和持续的功能性COL7蛋白表达。VYJUVEK™（B-VEC）预计将于2023年第三季度在美国上市。药融圈旗下，药融云数据www.pharnexcloud.com显示，欧洲药品管理局此前已授予B-VEC治疗DEB的孤儿药认定和优先药物资格，公司预计将于2023年下半年在欧洲启动正式的上市许可申请程序，并可能在2024年获得批准。该公司还与日本药品和医疗器械局合作研究B-VEC，并寻求在日本批准上市。2023年4月，日本厚生劳动省（MHLW）通知该公司，根据“卡塔赫纳法”（Cartagena Act），B-VEC被确认为可安全进口。随着“卡塔赫纳法”批准B-VEC的进口，公司计划在日本启动B-VEC的规模开放标签扩展研究，预计将于2025年初在日本获得批准。▲截图自药融云数据拯救“蝴蝶宝贝”营养不良性大疱性表皮松解症（DEB）是一种极其罕见且严重的遗传性皮肤病，由COL7A1基因突变引起，它编码VII型胶原蛋白（COL7），影响皮肤和粘膜组织。由于缺乏功能性COL7蛋白，患者皮肤的真皮（皮肤内层）与表皮（皮肤外层）的粘附被破坏，极其脆弱，轻微的擦碰就会导致水疱和撕裂，甚至可影响到胃肠道、口腔、眼睛等器官，开放性伤口引起复发性皮肤感染和纤维化，导致手指和脚趾融合，最终增加侵袭性皮肤癌的风险，如侵袭性鳞状细胞癌。这些患者被称为“蝴蝶宝贝”，形容患者皮肤像蝴蝶般脆弱。（纪录片《支离破碎的男孩》就描述了一位大疱性表皮松解症患者的故事）据统计，全球范围内大约有9000例DEB患者。目前，该病的治疗方法主要以专业的皮肤护理和避免皮肤机械损伤为主，慢性伤口管理、绷带、疼痛和感染控制，以及手术干预，导致每年的护理费用估计为20万至40万美元，且当前只有美国可以提供支持性护理服务。VYJUVEK™（B-VEC）作为全球首款且目前唯一一款治疗DEB的矫正疗法，无疑为这些患者带来了希望。据悉，该药物每瓶价格为2.425万美元，平均每位患者每年使用26瓶，每位患者每年治疗费用约为63.1万美元，经政府强制折扣后为48.5万美元。为了满足患者、护理人员和家属的需求，公司开发了个性化的支持项目Krystal Connect。该计划包括可以回答有关VYJUVEK的问题、验证健康益处、支持治疗计划和管理，以及为符合条件的患者提供有关经济援助的信息资源。此外，公司为了确保疾病的准确诊断，还推出了基因检测项目Decode DEB。基因治疗递送载体的突破在基因治疗药物开发过程中，递送系统是主要的核心与挑战之一，也是药物实现临床应用的重要基础。（相关阅读：核酸药物“淘金热”，递送系统成角逐“高地”）VYJUVEK™（B-VEC）的成功获批不仅是基因治疗领域的里程碑，也是非AAV（腺相关病毒）递送载体的里程碑。COL7A1基因的转录产物大小达到了约9 kb，为工程化基因治疗载体的开发提出了一大挑战。这样的大小超出了腺病毒和腺相关病毒等大部分病毒载体的荷载能力，COL7A1只能经过大量定向修饰后，在慢病毒和逆转录病毒载体中功能化表达。相比之下，HSV-1病毒（单纯疱疹病毒1型）的转基因有效载荷能力超过30 kb，且由于HSV-1载体是非整合的，因此不构成任何插入突变的风险，这些特性使HSV-1载体特别适合在体（In vivo）基因治疗。Krystal Biotech公司基于此开发了专有的可重复基因治疗平台，即皮肤靶向给药平台（STAR-D，Skin TARgeted Delivery platform），该平台由经改造的非整合、复制缺陷的工程化HSV-1载体和皮肤优化基因转移技术组成，利用HSV-1的独特特性克服了其他常用载体的荷载能力、免疫原性和潜在的安全问题，并可以有效地穿透广泛的皮肤细胞，适用于将一个或多个与皮肤病相关的治疗性基因引入患者体内。该技术平台优势包括：1）可以局部给药；2）对于分裂和非分裂细胞均具有转导能力，提高治疗性基因转移效率；3）非复制性，可被细胞分裂稀释，导致瞬时转基因表达；4）高有效载荷能力可容纳大的基因或多个基因；5）允许重复给药；6）不会插入或以其他方式破坏人类基因组。这些优势使得STAR-D平台成为直接和重复向皮肤递送治疗性基因的合适选择。1/2期（GEM-1/2）临床试验显示，B-VEC疗法介导的COL7A1转基因靶向适当的细胞，并引导功能性全长COL7蛋白（包括NC1和NC2结构域）在真皮-表皮基底膜正确位置的表达。发表在《新英格兰医学杂志》上的关键3期（GEM-3）临床试验数据显示，该试验在六个月时达到了伤口完全愈合的主要终点，在三个月时达到了伤口完全愈合的关键次要终点。B-VEC组患者在治疗六个月时有67.4%的伤口完全愈合，安慰剂组为21.6%；在治疗三个月时，B-VEC组患者有70.6%的伤口完全愈合，安慰剂组为19.7%。（相关阅读：3期临床成功，涨150%，这家Biotech的基因疗法获突破）▲图源：NEJM基于上述研究的结果，VYJUVEK™（B-VEC）外用凝胶获得美国FDA批准，用于治疗六个月或以上的隐性或显性DEB患者，由医疗保健专业人员在医疗保健专业机构（例如诊所）或家庭环境中使用。获得批准后，FDA还向Krystal Biotech公司颁发了罕见儿科疾病优先审查凭证（PRV）。成立18个月即IPO的基因治疗“新星”Krystal Biotech公司专注于为罕见疾病患者开发和商业化基因治疗药物，目标是开发易于使用的药物，以极大地改善罕见疾病和慢性病患者的生活。除了拥有基于工程化HSV-1的基因治疗技术平台之外，Krystal公司内部还拥有商业规模的符合CGMP的制造能力，从而支持产品的制造需求以及未来增长。公司创始人是在生物技术领域拥有丰富经验的Krish Krishnan和Suma Krishnan夫妇，从自筹资金组建Krystal Biotech到公司IPO，只花了18个月。药融圈旗下，药融云数据www.pharnexcloud.com显示，2016年4月，Krystal Biotech开始正式运营，并于2017年9月登陆纳斯达克（NASDAQ:KRYS），IPO募得资金4554万美元。2023年5月，Krystal Biotech在宣布VYJUVEK™（B-VEC）获批消息之后，随即完成1.6亿美元的私募股权融资，由Avoro Capital Advisors和Redmile Group领投，Braidwell LP和Frazier Life Sciences参与。截止目前，公司市值约31亿美元。该公司早前被Fierce Biotech评为2023年生物技术领域十大并购目标之一。Krystal Biotech公司当前的生物制药管线主要聚焦在皮肤科、呼吸科和眼科三个领域。除了VYJUVEK™（B-VEC）已获批之外，其他产品均处于在研阶段。▲Krystal Biotech产品管线（更新至2023年6月）在皮肤科领域，公司主要还开发了另两款局部凝胶制剂，分别针对不用的罕见皮肤疾病。KB105（inetagugene geperpavec）正在被开发用于治疗常染色体隐性遗传的先天性鱼鳞病（ARCI），该病是一种严重的罕见皮肤病，患者往往表现出终身明显的板状皮肤鳞屑，通常是深色，可覆盖整个身体。ARCI常由TGM1（转谷氨酰胺酶1）基因失活突变引起，该基因编码一种对皮肤屏障正常形成至关重要的蛋白质。KB105作为一种可重复的现成基因疗法，旨在局部应用于皮肤，递送两个TGM1基因的拷贝，从而在给药部位直接补充TGM1蛋白。药融云数据www.pharnexcloud.com显示，FDA和EMA已分别授予KB105孤儿药称号用于治疗TGM1缺陷型ARCI，FDA已授予KB105快速通道认定和罕见儿科疾病用药认定用于治疗TGM1-ARCI。目前，该药正在进行一项1/2期临床试验，预计将在2023年年中启动2期临床。KB104被开发用于治疗内瑟顿（Netherton）综合征，该病是一种罕见的常染色体隐性遗传性皮肤病，由SPINK5基因（由Kazal 5型丝氨酸蛋白酶抑制剂基因）突变引起，该基因编码一种表达于上皮和黏膜表面的丝氨酸蛋白酶抑制剂。患者因SPINK5基因突变，皮肤中的丝氨酸蛋白酶过度活化，引起不受控制的脱屑，导致皮肤屏障缺陷，特征是先天性鱼鳞病样红皮病、毛干缺陷、反复感染等。KB104旨在将SPINK5基因的两个拷贝递送到相关皮肤细胞，直接向皮肤补充功能性SPINK5，纠正脱屑并改善皮肤的屏障功能。公司预计将在2023下半年提交该药的IND申请，此前KB104已获得FDA授予的KB104罕见儿科疾病用药认定用于治疗内瑟顿综合征。在呼吸科领域，Krystal Biotech主要开发了两款吸入（雾化）制剂，同样是针对罕见疾病。KB407被开发用于治疗囊性纤维化（CF），该病是一种进行性遗传疾病，由囊性纤维化跨膜传导调节因子（CFTR）基因突变引起，患者分泌性气道上皮中缺乏功能性CFTR蛋白，引起Cl-、碳酸氢盐和硫氰酸盐分泌缺陷，加上Na+吸收和粘液产生增多，导致气道表面液体脱水和酸化，特征是反复肺部感染、气道分泌物增加，最终导致呼吸衰竭。KB407作为一种可重复的现成的基因疗法，旨在通过吸入（雾化）给药将两个全长CFTR转基因拷贝直接递送到气道上皮，诱导肺部全长正常CFTR蛋白表达。体外研究显示，KB407纠正了患者来源的3D肠道类器官中的CFTR缺陷，且与CFTR突变类型无关。目前，KB407正在美国和澳大利亚开展两项1期临床研究。此前FDA和EMA已分别授予KB407孤儿药称号用于治疗囊性纤维化，FDA已授予KB407罕见儿科疾病用药认定用于治疗囊性纤维化。KB408被开发用于治疗α-1抗胰蛋白酶缺乏症（AATD），该病是一种常染色体共显性遗传病，由蛋白酶抑制剂基因位点处的SERPINA1基因内发生等位基因突变所致，患者血清α-1-抗胰蛋白酶（AAT）水平低，导致进行性肺损伤和严重的呼吸功能不全，表现为慢性阻塞性肺病（COPD）和全腺泡性肺气肿等。KB408旨在递送编码正常人α-1-抗胰蛋白酶蛋白的SERPINA1转基因的两个拷贝，从而治疗AATD，公司预计将在2023年底提交IND申请。在眼科领域，Krystal Biotech开发了眼用的B-VEC，用于治疗DEB（营养不良性大疱性表皮松解症）的眼部并发症。在DEB患者中，很大一部分存在COL7缺乏相关的眼部并发症，表现为角膜擦伤、瘢痕和血管翳等，可导致进行性视力丧失甚至失明，在RDEB（隐性营养不良性大疱性表皮松解症）患者中，超过50%的患者存在眼部并发症。B-VEC眼部制剂旨在恢复DEB患者的局部COL7A1表达和眼部功能。在同情用药计划中，B-VEC眼部制剂显著改善了DEB患者眼部并发症，患者视力显著改善，公司计划与FDA召开会议以调整眼部制剂的进一步开发路径。这也表明了公司的基因治疗平台具有治疗多种眼部疾病的潜力。医美布局虽然目前Krystal Biotech的重点是开发基因疗法以治疗严重罕见疾病，但同时公司也在评估技术平台应用于更常见疾病和/或非遗传性疾病的潜力。2019年4月，Krystal Biotech在特拉华州注册成立全资子公司Jeune Aesthetics，借助公司技术平台的能力，该子公司专注于医美领域的产品开发，向皮肤细胞递送目标蛋白质以对抗皮肤老化。Jeune Aesthetics的领先产品KB301旨在通过皮内注射给药，递送编码3型胶原蛋白（COL3）的基因COL3A1以刺激皮肤的生物再生，从而对抗皮肤老化或受损迹象，目前正在积极开展1期临床试验。2022年3月，Jeune宣布了PEARL-1试验有效性队列中关于改善（上脸颊、下脸颊以及膝盖皮肤）细纹和皱纹的积极概念验证、安全性和有效性数据。2022年11月，Jeune公布了来自PEARL-1扩展队列的数据，显示在给予高剂量KB301后，效果的持久性长达9个月。2023年4月，Jeune完成了KB301的1期临床试验队列3研究中针对静止状态下的外眦纹（鱼尾纹，LCL）的首例患者给药，受试者将在KB301治疗后随访3个月，研究预计在2023年下半年完成。这项研究完成后，Jeune计划启动KB301针对LCL的2期临床研究。此外，如上图所示，Jeune还有其他几种处于临床前不同开发阶段的医美候选产品。财务状况截至2023年3月底，Krystal Biotech拥有现金、现金等价物和短期投资共约3.504亿美元，足以支持公司未来至少12个月的运营开支。由于尚未有产品业绩产生，公司自正式运营以来一直处于亏损状态，截至2023年3月31日，累计赤字为3.261亿美元。2022年、2021年和2020年，公司净亏损分别为1.4亿美元、6960万美元和3220万美元。2023年第一季度净亏损4530万美元。不过随着已获批产品销售工作的推进，以及潜在的对外合作和许可，公司未来或将从产品销售、产品销售特许、里程碑或者其他预付款中获得收入。2022全年，公司研发费用为4246万美元，一般与管理费用为7774万美元，与上一年度相比均有增长。2023年第一季度，公司研发费用为1229万美元，一般与管理费用为2404万美元，与去年同期相比均有增长。其中的诉讼和解费用来源于早前Krystal Biotech与基因治疗公司PeriphaGen的商业秘密纠纷（PeriphaGen使用HSV-1载体用于神经系统疾病等）。2020年5月，PeriphaGen起诉Krystal Biotech违反合同和盗用商业秘密，主要涉及Krystal的基因递送载体骨架和STAR-D技术平台。2020年6月，Krystal否认指控，提起反诉，并指控PeriphaGen违约。2022年4月，两家公司签订最终和解协议，Krystal向PeriphaGen支付2500万美元的预付款，包括解除PeriphaGen公司商业秘密诉讼中的所有索赔；收购PeriphaGen的生物材料和皮肤科资产；PeriphaGen授予Krystal在皮肤科领域的应用许可。在美国FDA批准Krystal首款产品之后，公司向PeriphaGen支付额外的1250万美元；在累计销售总额分别达到1亿美元、2亿美元和3亿美元时，再向PeriphaGen支付3次额外的1250万美元里程碑付款。未来计划对于未来机会，Krystal Biotech认为公司专有基因治疗递送载体的重复给药能力，以及较大的有效荷载能力，能够实现多个基因和其他效应物的递送，从而治疗非单基因皮肤病，如牛皮癣和特应性皮炎，以及不一定是遗传基因缺陷疾病的疗法开发，如慢性伤口。例如，作为概念验证，Krystal Biotech已经生成了一个设计用于递送抗炎抗体的载体库。其中有一款载体已在特应性皮炎的动物模型中进行了评估，且证实了抗体的表达并观察到疗效。若能够成功开发出治疗这些非罕见疾病的候选药物，Krystal Biotech计划寻求对外合作以实现候选产品的进一步开发和潜在的商业化。此文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场参考：NMPA/CDE；药融云数据www.pharnexcloud.comFDA/EMA/PMDA；相关公司公开披露（正文图片均来自企业官方，除非另有说明）；https://www.krystalbio.com/；https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-receives-fda-approval-first-ever-redosable-gene；https://www-nature-com.libproxy1.nus.edu.sg/articles/s41591-022-01737-y；https://www-nejm-org.libproxy1.nus.edu.sg/doi/full/10.1056/NEJMoa2206663；https://www.fiercebiotech.com/special-reports/top-10-ma-targets-biotech-2023；https://www.smartbusinessdealmakers.com/articles/topic/krystal-biotech-krish-krishnan-startup-ipo/；等等。「 会议推荐」点分享点点赞点在看