A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety and Efficacy of HMI-103 Administered Intravenously in Adult Participants With Classical PKU Due to PAH Deficiency

This is an open-label, sequential ascending dose-escalation, Phase 1 study to evaluate the safety and efficacy of a single intravenous (I.V.) administration of HMI-103, a gene editing development candidate, in adult participants aged 18 to 55 years, inclusive, with classical PKU due to PAH deficiency who have uncontrolled disease despite Phe restricted dietary management.

开始日期2022-06-03

申办/合作机构

Homology Medicines, Inc.

100 项与 HMI-103 相关的临床结果

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100 项与 HMI-103 相关的转化医学

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100 项与 HMI-103 相关的专利（医药）

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项与 HMI-103 相关的新闻（医药）

2023-11-16

·PRNewswire

Q32 Bio and Homology Medicines Announce Merger Agreement

--The combined company will operate as Q32 Bio Inc., advancing the development of Q32 Bio's two clinical development candidates, bempikibart (ADX-914) in Phase 2 for the treatment of atopic dermatitis (AD) and alopecia areata (AA), and ADX-097 entering Phase 2 for the treatment of complement disorders----Q32 Bio has re-acquired worldwide development and commercial rights to bempikibart, an anti-IL-7Rα antibody inhibiting IL-7 and TSLP-mediated signaling, and remains on-track to report multiple topline Phase 2 results in 2H'24 ----Concurrent $42 million private placement investment with new and existing investors supports clinical development through multiple milestones, including key Phase 2 readouts for bempikibart, initial ADX-097 proof-of-concept data by year-end 2024 and ADX-097 topline results in 2H'25 ----Combined company's cash balance expected to be approximately $115 million at close, providing cash runway to mid-2026-- WALTHAM, Mass. and BEDFORD, Mass., Nov. 16, 2023 /PRNewswire/ -- Q32 Bio Inc., a clinical stage biotechnology company developing biologic therapeutics to restore immune homeostasis, and Homology Medicines, Inc. (Nasdaq: FIXX), today announced they have entered into a definitive merger agreement to combine the companies in an all-stock transaction. The combined company will focus on advancing Q32 Bio's wholly owned clinical development candidates for the treatment of autoimmune and inflammatory diseases. Upon completion of the merger, the combined company will operate as Q32 Bio, headquartered in Waltham, Massachusetts, and is expected to trade under the Nasdaq ticker symbol "QTTB". Continue Reading Homology Medicines, Inc. In support of the merger agreement, Q32 Bio has entered into an agreement for a $42 million private placement with participation from existing and new investors including OrbiMed, Atlas Venture, Abingworth, Bristol Myers Squibb, Acorn Bioventures, Osage University Partners (OUP), CU Healthcare Innovation Fund, Sanofi Ventures, Agent Capital and other undisclosed investors. "The proposed merger with Homology Medicines and concurrent private placement is expected to provide Q32 Bio with the capital to drive development of our autoimmune and inflammatory pipeline through multiple clinical milestones," said Jodie Morrison, Chief Executive Officer of Q32 Bio. "This funding is expected to enable us to deliver two Phase 2 readouts for bempikibart in the second half of 2024, proof-of-concept data for ADX-097, a tissue-targeted inhibitor of complement activation, by year-end 2024, and topline ADX-097 clinical results in the second half of 2025." "Following a comprehensive assessment of our strategic options, management and the Board of Directors believe the merger with Q32 Bio is in the best interest of our shareholders," said Albert Seymour, President and Chief Executive Officer of Homology Medicines. "The Q32 Bio management team's extensive track record, deep biopharmaceutical expertise and the potential of its clinical development pipeline provide a compelling opportunity to deliver meaningful treatments to patients with critical unmet needs." Proceeds from the proposed transactions will be used to advance the clinical development of Q32 Bio's two wholly owned assets, bempikibart (ADX-914), for which Q32 Bio earlier today announced it regained all rights from Amgen, and ADX-097. Bempikibart, Q32 Bio's lead program, is a fully human anti-IL-7Rα antibody that re-regulates adaptive immune function by blocking signaling mediated by both IL-7 and TSLP and is currently being evaluated in two Phase 2 trials, with one clinical trial evaluating the use in atopic dermatitis (AD) and one evaluating the use in alopecia areata (AA). All data from the Phase 2 trials remain blinded and Q32 Bio remains on track to report topline Phase 2 results in the second half of 2024. ADX-097 is based on a novel platform enabling tissue-targeted regulation of the complement system without long-term systemic blockade, a key differentiator from current complement therapeutics. Q32 Bio recently completed a first-in-human, Phase 1 ascending dose clinical study of ADX-097 in healthy volunteers. Results from the Phase 1 clinical trial demonstrated a favorable tolerability and immunogenicity profile across all single and multiple dose cohorts and weekly subcutaneous dosing met exposures for predicted complete complement inhibition in the tissue with no systemic inhibition. Q32 Bio will be commencing an open-label Phase 2 basket clinical trial, with initial data expected by year-end 2024, and a Phase 2 clinical trial in ANCA-Associated Vasculitis (AAV), with topline results from the AAV and basket trials expected in the second half of 2025. About the Proposed Merger Under the terms of the merger agreement, Homology Medicines will issue to pre-merger Q32 Bio stockholders shares of Homology Medicines common stock as merger consideration in exchange for the cancellation of shares of capital stock of Q32 Bio, and Q32 Bio will become a wholly owned subsidiary of Homology Medicines. Stockholders of Q32 Bio will receive newly issued shares of Homology Medicines common stock pursuant to a formula set forth in the merger agreement. Pre-merger Homology Medicines stockholders are expected to own approximately 25% of the combined company and pre-merger Q32 Bio stockholders (including those purchasing Q32 Bio shares in the concurrent private financing discussed above) are expected to own approximately 75% of the combined company. The percentage of the combined company that pre-merger Q32 Bio stockholders and pre-merger Homology Medicines will own upon the closing of the merger is further subject to adjustment based on the amount of Homology Medicine's net cash at the time of closing. In connection with the closing of the proposed transactions, Homology Medicines stockholders will also be issued a contingent value right (CVR) representing the right to receive certain payments from proceeds received by the combined company, if any, related to dispositions of Homology Medicines' pre-transaction legacy assets. Homology Medicines has discontinued development of its R&D programs, including HMI-103 for the treatment of PKU, and has been exploring strategic alternatives for its programs and platform technology. If Homology Medicines has not otherwise disposed of its ownership position in Oxford Biomedica Solutions, LLC (Oxford Solutions), a contract development and manufacturing organization (CDMO) jointly established by Homology Medicines and Oxford Biomedica plc, and monetized its development programs, including HMI-103 for the treatment of PKU, Homology Medicines stockholders of record will be issued a CVR for each outstanding share of Homology Medicines common stock held by such Homology Medicines stockholder prior to the closing of the proposed merger. The CVR would represent the right to receive certain cash payments from proceeds received by Homology Medicines related to the sale or license of its development programs and platform technology and the exercise of a put/call option or other sale or disposition of Homology Medicines' minority ownership position in Oxford Solutions. The merger agreement has been approved by the boards of directors of both companies. Additional information about the transaction will be provided in a Current Report on Form 8-K that will be filed by Homology Medicines with the Securities and Exchange Commission (SEC) and will be available at . Leerink Partners is serving as the exclusive financial advisor to Q32 Bio. Leerink Partners and Piper Sandler are serving as placement agents for Q32 Bio's planned private placement. Goodwin Procter LLP is serving as legal counsel to Q32 Bio. TD Cowen is serving as the exclusive financial advisor and Latham & Watkins LLP is serving as legal counsel to Homology Medicines. Management and Organization Upon closing of the proposed transaction, the combined company will be led by current members of the Q32 Bio leadership team including: Jodie Morrison, Chief Executive Officer Shelia Violette, PhD, Founder & Chief Scientific Officer Jason Campagna, MD, PhD, Chief Medical Officer Saul Fink, PhD, Chief Technology Officer Maria Marzilli, MPH, Executive Vice President, Corporate Strategy & Program Operations David Appugliese, JD, Senior Vice President, Head of People The Board of Directors of the combined company is expected to be comprised of nine members, consisting of seven members designated by Q32 Bio and two members designated by Homology Medicines. The transaction has been approved by the Board of Directors of each company and is expected to close in the first quarter of 2024, subject to customary closing conditions, including the approval of the transaction by the stockholders of each company. About Q32 Bio Q32 Bio is a clinical stage biotechnology company developing biologic therapeutics targeting potent regulators of the innate and adaptive immune systems to re-balance immunity in autoimmune and inflammatory diseases. Q32 Bio's lead programs, focused on the IL-7 / TSLP receptor pathways and complement system, address immune dysregulation to help patients take back control of their lives. Q32 Bio's program for adaptive immunity, bempikibart (ADX-914), is a fully human anti-IL-7Rα antibody that re-regulates adaptive immune function for the treatment of autoimmune diseases. It is being evaluated in two Phase 2 trials for the treatment of atopic dermatitis and alopecia areata. The IL-7 and TSLP pathways have been genetically and biologically implicated in driving several T cell-mediated pathological processes in numerous autoimmune diseases. Q32 Bio's program for innate immunity, ADX-097, is based on a novel platform enabling tissue-targeted regulation of the complement system without long-term systemic blockade – a key differentiator versus current complement therapeutics. Q32 Bio has recently completed a first-in-human, Phase 1 ascending dose clinical study of ADX-097 in healthy volunteers. About Homology Medicines Homology Medicines, Inc. is a clinical-stage genetic medicines company historically focused on transforming the lives of patients suffering from rare diseases by addressing the underlying cause of the disease. Homology Medicines has gene editing and gene therapy clinical-stage programs in PKU and Hunter syndrome (MPS II), a preclinical pipeline that includes a gene therapy candidate for metachromatic leukodystrophy and a GTx-mAb (vectorized antibody) candidate for paroxysmal nocturnal hemoglobinuria, as well as intellectual property on its family of 15 adeno-associated viruses (AAVHSCs). Homology Medicines is not currently pursuing further development of these programs and is pursuing strategic options for the Company and its programs and platform technology. Additionally, the Company has an ownership stake in Oxford Solutions, an AAV manufacturing company based on Homology Medicines' internal process development and manufacturing formed as a joint venture between Homology Medicines and Oxford Biomedica plc. Cautionary Statement Regarding Forward-Looking Statements This communication contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, including statements regarding the proposed transaction involving Homology Medicines and Q32 Bio, including the conditions to, and timing of, closing of the proposed transaction, the location and management of the combined company, the percentage ownership of the combined company, and the parties' ability to consummate the proposed transaction and private placement financing, including the intended use of net proceeds from the private placement financing and the expected timing of closing and completion of the private placement financing, the composition of the Board of Directors of the combined company, the expected issuance of the CVR and the contingent payments contemplated by the CVR, the combined company's expected cash and the sufficiency of the combined company's cash, cash equivalents and short-term investments to fund operations into mid-2026, the listing of the combined company's shares on Nasdaq, the expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of Q32 Bio's product candidates, including bempikibart and ADX-097, and anticipated milestones and timing, among others. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "expect," "anticipate," "plan," "likely," "believe," "estimate," "project," "intend," and other similar expressions among others. Statements that are not historical facts are forward-looking statements. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: (i) the risk that the conditions to the closing of the proposed transaction are not satisfied, including the failure to timely or at all obtain stockholder approval for the proposed transaction or the failure to timely or at all obtain any required regulatory clearances; (ii) uncertainties as to the timing of the consummation of the proposed transaction and the ability of each of Homology Medicines and Q32 Bio to consummate the proposed transaction; (iii) the ability of Homology Medicines and Q32 Bio to integrate their businesses successfully and to achieve anticipated synergies; (iv) the possibility that other anticipated benefits of the proposed transaction will not be realized, including without limitation, anticipated revenues, expenses, earnings and other financial results, and growth and expansion of the combined company's operations, and the anticipated tax treatment of the combination; (v) potential litigation relating to the proposed transaction that could be instituted against Homology Medicines, Q32 Bio or their respective directors; (vi) possible disruptions from the proposed transaction that could harm Homology Medicines' and/or Q32 Bio's respective businesses; (vii) the ability of Homology Medicines and Q32 Bio to retain, attract and hire key personnel; (viii) potential adverse reactions or changes to relationships with customers, employees, suppliers or other parties resulting from the announcement or completion of the proposed transaction; (ix) potential business uncertainty, including changes to existing business relationships, during the pendency of the proposed transaction that could affect Homology Medicines' or Q32 Bio's financial performance; (x) certain restrictions during the pendency of the proposed transaction that may impact Homology Medicines' or Q32 Bio's ability to pursue certain business opportunities or strategic transactions; (xi) the combined company's need for additional funding, which may not be available; (xii) failure to identify additional product candidates and develop or commercialize marketable products; (xiii) the early stage of the combined company's development efforts; (xiv) potential unforeseen events during clinical trials could cause delays or other adverse consequences; (xv) risks relating to the regulatory approval process; (xvi) interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data; (xvii) Q32 Bio's product candidates may cause serious adverse side effects; (xviii) inability to maintain our collaborations, or the failure of these collaborations; (xix) the combined company's reliance on third parties, including for the manufacture of materials for our research programs, preclinical and clinical studies; (xx) failure to obtain U.S. or international marketing approval; (xxi) ongoing regulatory obligations; effects of significant competition; (xxii) unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; (xxiii) product liability lawsuits; (xxiv) securities class action litigation; (xxv) the impact of the COVID-19 pandemic and general economic conditions on our business and operations, including the combined company's preclinical studies and clinical trials; (xxvi) the possibility of system failures or security breaches; risks relating to intellectual property; (xxvii) significant costs incurred as a result of operating as a public company; and (xxviii) such other factors as are set forth in Homology Medicines' periodic public filings with the SEC, including but not limited to those described under the heading "Risk Factors" in Homology Medicines' Form 10-Q for the period ended September 30, 2023. Homology Medicines can give no assurance that the conditions to the proposed transaction will be satisfied. Except as required by applicable law, Homology Medicines undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. Important Information about the Merger and Where to Find It This communication relates to a proposed transaction between Homology Medicines and Q32 Bio. In connection with the proposed transaction, Homology Medicines intends to file with the SEC a registration statement on Form S-4 that will include a proxy statement of Homology Medicines and that will constitute a prospectus with respect to shares of Homology Medicines' common stock to be issued in the proposed transaction (Proxy Statement/Prospectus). Homology Medicines may also file other documents with the SEC regarding the proposed transaction. This document is not a substitute for the Proxy Statement/Prospectus or any other document which Homology Medicines may file with the SEC. INVESTORS, Q32 BIO STOCKHOLDERS AND HOMOLOGY MEDICINES STOCKHOLDERS ARE URGED TO READ THE PROXY STATEMENT/PROSPECTUS AND ANY OTHER RELEVANT DOCUMENTS THAT ARE OR WILL BE FILED BY HOMOLOGY MEDICINES WITH THE SEC, AS WELL AS ANY AMENDMENTS OR SUPPLEMENTS TO THESE DOCUMENTS, CAREFULLY AND IN THEIR ENTIRETY BECAUSE THEY CONTAIN OR WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION AND RELATED MATTERS. Investors, Q32 Bio stockholders and Homology Medicines stockholders will also be able to obtain free copies of the Proxy Statement/Prospectus (when available) and other documents containing important information about Homology Medicines, Q32 Bio and the proposed transaction that are or will be filed with the SEC by Homology Medicines through the website maintained by the SEC at . Copies of the documents filed with the SEC by Homology Medicines will also be available free of charge on Homology Medicines' website at or by contacting Homology Medicines' investor relations department by email at [email protected]. No Offer or Solicitation This communication is not intended to and shall not constitute an offer to buy or sell or the solicitation of an offer to buy or sell any securities, or a solicitation of any vote or approval, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. No offer of securities shall be made, except by means of a prospectus meeting the requirements of Section 10 of the Securities Act. Participants in the Solicitation Homology Medicines and certain of its directors and executive officers may be deemed under SEC rules to be participants in the solicitation of proxies of Homology Medicines stockholders in connection with the proposed transaction. Information regarding the persons who may, under SEC rules, be deemed participants in the solicitation of proxies to Homology Medicines' stockholders in connection with the proposed transaction will be set forth in the Proxy Statement/Prospectus on Form S-4 for the proposed transaction, which is expected to be filed with the SEC by Homology Medicines. Investors and security holders of Q32 Bio and Homology Medicines are urged to read the Proxy Statement/Prospectus and other relevant documents that will be filed with the SEC by Homology Medicines carefully and in their entirety when they become available because they will contain important information about the proposed transaction. Investors and security holders will be able to obtain free copies of the Proxy Statement/Prospectus and other documents containing important information about Q32 Bio and Homology Medicines through the website maintained by the SEC at . Copies of the documents filed with the SEC by Homology Medicines can be obtained free of charge by directing a written request to Homology Medicines, Inc., One Patriots Park, Bedford, MA 01730. Contacts: For Q32 Bio: Investors: Brendan Burns Media: Sarah Sutton Argot Partners 212.600.1902 [email protected] For Homology Medicines: Brad Smith Chief Financial and Business Officer 781-691-3519 [email protected] SOURCE Q32 Bio

临床1期临床2期临床结果并购

2023-11-14

·GlobeNewswire-Health Care

Homology Medicines Reports Third Quarter 2023 Financial Results

- Continuing to Evaluate Strategic Options for the Company and the Pipeline of Genetic Medicines, including HMI-103 - BEDFORD, Mass., Nov. 14, 2023 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today third quarter 2023 financial results and highlighted recent updates. Homology recently shared a summary of safety and efficacy data on the first dose cohort of the pheEDIT clinical trial evaluating the Company’s HMI-103 gene editing candidate for the treatment of phenylketonuria (PKU). Despite the encouraging HMI-103 clinical data, based on the current financing environment and the anticipated clinical development timeline, Homology announced in July 2023 that it would not pursue any further development of its programs, including HMI-103, and instituted a related workforce reduction. Homology further announced that it is evaluating strategic options for the Company, its development programs, including HMI-103, and its platform technology. The Company retained TD Cowen as its strategic financial advisor and continues to productively advance the process of assessing strategic options. Third Quarter 2023 Financial Results As of September 30, 2023, Homology had approximately $103.3 million in cash, cash equivalents and short-term investments. Based on management’s current projections, which include the impact of not further developing any of its research and development programs and the recent workforce reduction of approximately 80 employees, Homology believes it has sufficient cash resources to fund operations for at least one year.Net loss for the quarter ended September 30, 2023 was $(33.0) million or $(0.57) per share, compared to a net loss of $(33.7) million or $(0.59) per share for the quarter ended September 30, 2022.There was no collaboration revenue for the quarter ended September 30, 2023, compared to $0.8 million for the quarter ended September 30, 2022. Collaboration revenue for the quarter ended September 30, 2022 reflected revenue recognized under the Company’s Stock Purchase Agreement with Pfizer. The Company previously granted Pfizer a right of first refusal to negotiate a potential collaboration on the development and commercialization of HMI-102 and HMI-103, as well as information sharing rights, both of which expired on May 9, 2023.Total operating expenses for the quarter ended September 30, 2023 were $31.0 million, compared to $33.7 million for the quarter ended September 30, 2022, and consisted of research and development expenses and general and administrative expenses. Operating expenses for the quarter ended September 30, 2023 also included restructuring and other charges.Research and development expenses for the quarter ended September 30, 2023 were $17.5 million, compared to $25.9 million for the quarter ended September 30, 2022. Research and development expenses decreased due to lower employee-related costs as a result of the workforce reduction in the third quarter of 2023, and lower clinical trial costs, partially offset by higher manufacturing and process development costs as the Company continues to wind down its remaining commitments to Oxford Biomedica Solutions, the CDMO established as a joint venture with Oxford Biomedica in March 2022.General and administrative expenses for the quarter ended September 30, 2023 were $6.8 million, compared to $7.8 million for the quarter ended September 30, 2022. General and administrative expenses decreased as a result of lower employee-related costs due to the workforce reduction and lower consulting and market research costs.Restructuring and other charges totaled $6.6 million for the quarter ended September 30, 2023 and primarily related to the workforce reduction of approximately 80 employees, effective August 3, 2023. There were no such charges in the quarter ended September 30, 2022. About Homology Medicines, Inc. Homology Medicines, Inc. is a clinical-stage genetic medicines company historically focused on transforming the lives of patients suffering from rare diseases by addressing the underlying cause of the disease. Homology has gene editing and gene therapy clinical-stage programs in PKU and Hunter syndrome (MPS II), a preclinical pipeline that includes a gene therapy candidate for metachromatic leukodystrophy and a GTx-mAb (vectorized antibody) candidate for paroxysmal nocturnal hemoglobinuria, as well as intellectual property on its family of 15 adeno-associated viruses (AAVHSCs). Homology is not currently pursuing further development of these programs and is pursuing strategic options for the Company and its programs and platform technology. Additionally, the Company has a twenty percent stake in Oxford Biomedica Solutions, an AAV manufacturing company based on Homology’s internal process development and manufacturing formed as a joint venture between Homology and Oxford Biomedica plc. For more information, visit www.homologymedicines.com. Forward-Looking StatementsThis press release contains forward-looking statements. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding: the timing and anticipated benefits and costs associated with our recent reduction in force, related corporate restructuring efforts and plans to evaluate strategic options; the expected financial and operational impacts of our restructuring initiatives; our future results of operations and financial position and the impact of the current economic environment on our business; and the sufficiency of our cash, cash equivalents and short-term investments to fund our operations. The words “believe,” “may,” “will,” “estimate,” “potential,” “continue,” “anticipate,” “intend,” “expect,” “could,” “would,” “project,” “plan,” “target,” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements use these words or expressions. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; any financial or strategic option we pursue may not be successful; our decision to discontinue further program development efforts may not result in the anticipated savings for the Company and may adversely affect our business; our recent reduction in force undertaken to reduce our ongoing operating expenses may not result in our intended outcomes and may yield unintended consequences as well as additional costs; should we resume development of our product candidates, potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process assuming we resume development of our product candidates; interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data assuming we resume development of our product candidates; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties, including for the manufacture of materials for our research programs, preclinical and clinical studies assuming we resume development of our product candidates; failure to obtain U.S. or international marketing approval assuming we resume development of our product candidates; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; securities class action litigation; the impact of the COVID-19 pandemic and general economic conditions on our business and operations, including our preclinical studies and clinical trials; failure to attract, retain and motivate qualified personnel in the future; the possibility of system failures or security breaches; risks relating to intellectual property; and significant costs incurred as a result of operating as a public company. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 and our other filings with the Securities and Exchange Commission could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. - Financial Tables Follow - HOMOLOGY MEDICINES, INC.CONDENSED CONSOLIDATED BALANCE SHEETS(in thousands)(Unaudited) As of September 30, 2023 December 31, 2022Cash, cash equivalents and short-term investments$103,298 $175,026 Equity method investment 13,957 25,814 Assets held for sale 314 — Property and equipment, net — 1,078 Right-of-use assets 19,471 20,563 Other assets 3,023 5,989 Total assets$140,063 $228,470 Accounts payable, accrued expenses and other liabilities$23,514 $19,859 Operating lease liabilities 28,338 29,477 Deferred revenue — 1,156 Stockholders' equity 88,211 177,978 Total liabilities and stockholders' equity$140,063 $228,470 HOMOLOGY MEDICINES, INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(in thousands, except share and per share amounts)(Unaudited) Three months ended September 30, Nine months ended September 30, 2023 2022 2023 2022 Collaboration revenue$— $802 $1,156 $2,406 Operating expenses: Research and development 17,519 25,854 60,489 71,202 General and administrative 6,842 7,810 23,355 29,991 Restructuring and other charges 6,640 — 6,640 — Total operating expenses 31,001 33,664 90,484 101,193 Loss from operations (31,001) (32,862) (89,328) (98,787)Other income: Gain on sale of business — — — 131,249 Interest income 1,423 1,269 4,403 1,775 Total other income 1,423 1,269 4,403 133,024 Income (loss) before income taxes (29,578) (31,593) (84,925) 34,237 Benefit from (provision for) income taxes — 46 — (816)Loss from equity method investment (3,376) (2,179) (11,917) (4,131)Net income (loss)$(32,954) $(33,726) $(96,842) $29,290 Net income (loss) per share-basic$(0.57) $(0.59) $(1.68) $0.51 Net income (loss) per share-diluted$(0.57) $(0.59) $(1.68) $0.51 Weighted-average common shares outstanding-basic 57,853,132 57,447,192 57,788,755 57,372,399 Weighted-average common shares outstanding-diluted 57,853,132 57,447,192 57,788,755 57,901,298 Company Contact:Brad SmithChief Financial and Business Officer781-691-3519bsmith@homologymedicines.com

财报基因疗法高管变更

2023-11-03

·FierceBiotech

Researchers cover bases with 2 different gene editing modalities to treat rare disease

While it wasn't possible to see which form of gene editing was better for treating PKU, the researchers plan to keep optimizing both methods and eventually take at least one to the clinic. Two new studies offer more validation that prime editing and base editing have the potential to permanently fix a gene variant associated with the rare disease phenylketonuria. In two separate papers published Nov. 2 in The American Journal of Human Genetics and Human Genetics and Genomic Advances, researchers at the University of Pennsylvania showed that prime and base editing could each repair the gene mutation that leads to PKU. This reversed the resulting pathology in both cases, correcting levels of a key protein enough to keep mice with PKU healthy. The data was also presented the same day at the American Society of Human Genetics' annual meeting. “This research…demonstrates the feasibility of using gene editing to permanently correct the most common genetic variant associated with this condition,” Kiran Musunuru, M.D., Ph.D., a senior author on both studies, said in a press release. “While there are still challenges to overcome, these findings open the door to potential new treatments that could significantly improve the lives of PKU patients.” While PKU is rare, it can be debilitating. The condition is caused by mutations in a gene called PAH, which encodes a liver enzyme by the same name to metabolize the amino acid phenylalanine. In PKU, mutations in PAH prevent it from encoding the enzyme. With nothing to break it down, phenylalanine builds up in the blood and brain, putting patients at risk of permanent brain damage if levels get too high. PKU is most often diagnosed in infancy and requires lifelong dietary restrictions to keep phenylalanine levels in check. While the past decade has seen new strides in drug treatments—such as BioMarin’s drug Kuvan, which may eventually be joined by a competitor from PTC Therapeutics—pharmaceutical interventions don’t work for everyone. Even when they are effective, patients must still avoid foods that are high in protein. As gene editing technology becomes more accessible, companies have looked for better solutions. BioMarin’s gene therapy candidate, BMN 307, is currently in a phase 1/2 clinical trial. Until recently, so was Homology Medicine’s HMI-103. While the nuances of BioMarin’s and Homology’s approaches differ, they both involve integrating a new gene sequence in the PAH gene so it produces the enzyme efficiently again. That’s different from base and prime editing, which alters the mutation itself. “To borrow an analogy from [CRISPR researcher] Fyodor Urnov, if you have a flat tire on your car, and you’re only on three tires, standard gene editing is like sticking an extra wheel on your car and hoping it works well,” Musunuru told Fierce Biotech Research in an interview. “Whereas base and prime editing is actually replacing the flat tire—you’re back to your normal four tires in the right places, and your car is going to work as well as it did before.” Both of the Musunuru lab’s new studies focused on a severe form of PKU that stems from the missense mutation PAH c.1222C>T, where a cytosine nucleotide has been incorrectly replaced by a tyrosine nucleotide in the PAH gene. In the prime editing study, which appears in The American Journal of Human Genetics, the researchers started by verifying that patients with that mutation had poor control over phenylalanine levels, then showed it was possible to use prime editing to correct the mutation in human liver cells. They then proceeded to test the approach in humanized mouse models of PKU, delivering the therapy via an adeno-associated viral vector, or AAV. Delivering the prime editors to the mice’s livers reduced phenylalanine to normal levels in all of them within around three weeks of treatment, with no adverse effects on their liver function. This was the case even in mice with only one copy of the alleles the researchers were editing, a good sign of the therapy’s potency. In the second study, published in Human Genetics and Genomic Advances, the researchers tested base editors delivered in a newer lipid nanoparticle, or LNP, delivery system that’s similar to the one used in the mRNA vaccines for COVID-19. LNP delivery is an active area of research in the gene therapy space, as the approach offers several advantages over AAVs—including a lower risk of immune-related side effects, Musunuru explained.“We were doing [AAVs] in the 2010s, but it’s the 2020s,” he said. “We have better ways of doing this now.” Following the same trajectory as in the prime editor study, the researchers first demonstrated that the base editors could correct the mutation in liver cells, then moved to mice. In this case, the treatment worked much more rapidly: Phenylalanine levels were reduced to normal within just 48 hours of administration in all of the treated mice. While the researchers didn’t monitor them long-term, previous studies using a similar approach have shown that the changes endure for at least six months, the researchers noted in their paper. It wasn’t possible to compare the editing efficiency of the prime editors and the base editors head to head because they were delivered via different methods—and delivering prime editors in lipid nanoparticles isn’t ready for prime time, based on his lab’s work, Musunuru said. While prime editing is more versatile than base editing, it’s also more complex and takes longer to complete. Although both AAVs and the LNP delivery system use guide RNA, the one in the LNPs works in short bursts of activity then breaks down, so it might not be sticking around long enough for editing to take place. Size might be another factor, Musunuru added. Prime editors are larger than base editors, so the guide RNA used with them is bigger as well—and creates a bigger challenge for packing it into LNPs, he said. “I’m sure we’ll eventually get to the point that lipid nanoparticles work as reliably well with prime editors as they currently do with base editors, but it will require quite a bit of optimization,” he said. Meanwhile, the base editors in LNPs are closer to being ready to study in humans, though there’s still more work to be done, Musunuru said. On top of that, his lab is working on figuring out how to make prime and base editing work on a variety of mutations. He’s especially interested in developing “plug-and-play” prime and base editors that can be useful even for very rare forms of PKU, as well as other diseases. “We’d like to be able to treat patients who have their own unique mutations—really get to the point where we can craft a personalized editing therapy for any patient in need,” Musunuru said.