Waldenstrom Macroglobulinemia

WORCESTER, Mass., March 11, 2024 (GLOBE NEWSWIRE) -- Mustang Bio, Inc. (“Mustang” or the “Company”) (Nasdaq: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for difficult-to-treat cancers and rare genetic diseases, today announced financial results and recent corporate highlights for the full-year ended December 31, 2023. "2023 was an exciting year for Mustang filled with many highlights, including compelling interim data from Mustang’s multicenter Phase 1/2 clinical trial of MB-106 presented at the 2023 American Society of Hematology Annual Meeting, which builds upon the stellar data presented earlier in the year from the MB-106 Phase 1/2 single institution clinical trial conducted at Fred Hutch. In both the multicenter Phase 1/2 trial and the single institution Phase 1/2 trial, the observed deepening and durability of responses are very gratifying. We believe the CAR T-cell persistence of up to 3 years in the original single institution trial at Fred Hutch and up to 1 year in the current Mustang-sponsored multicenter trial are important potential contributors to the deepening and durability of responses," said Manuel Litchman, M.D., President and Chief Executive Officer of Mustang. "We plan to move ahead with the first ever registrational CAR-T trial focused on relapsed or refractory Waldenstrom macroglobulinemia (“WM”), a subtype of indolent lymphoma with no FDA-approved therapy or standard of care in the third-line setting and no FDA-approved CAR-T for any line of therapy. We expect to treat the first patient in the second half of 2024, which could enable topline results in the second half of 2026. In order to facilitate interactions with the FDA throughout this process, we anticipate requesting Regenerative Medicine Advanced Therapy (‘RMAT’) designation for indolent lymphoma – which includes WM – from the FDA in the first half of 2024. Advantages of the RMAT designation include all the benefits of the Fast Track and Breakthrough Therapy Designation programs, including early interactions with FDA.” Dr. Litchman continued, “Additionally, we are evaluating the potential to initiate a first-ever Phase 1 multicenter clinical trial at City of Hope (“COH”) and the University of Alabama at Birmingham (“UAB”) to assess the safety, tolerability and efficacy of MB-109, a novel combination of MB-101 (IL13Rα2‐targeted CAR T-cell therapy) and MB-108 (HSV-1 oncolytic virus) in adult patients with recurrent GBM and high-grade astrocytomas that express IL13Rα2 on the surface of the tumor cells. The combination leverages MB-108 to reshape the tumor microenvironment (“TME”) and make cold tumors “hot,” which could potentially enhance the clinical effect of MB-101 CAR T-cell therapy. As per a recent publication in Nature Medicine, two patients treated solely with MB-101 who had high levels of intratumoral CD3+ T-cells pre-therapy (i.e., “hot” tumors) achieved complete responses lasting 7.5 and 66+ months, respectively. Also noteworthy is our continued work with the Mayo Clinic to progress our exclusively licensed novel in vivo CAR-T technology platform, for which we anticipate an upcoming publication of proof-of-concept research in a murine tumor model in 2024." Financial Results: As of December 31, 2023, Mustang’s cash and cash equivalents and restricted cash totaled $7.0 million, compared to $76.7 million as of December 31, 2022, a decrease of $69.7 million year-over-year. In 2023 Mustang made a $30.4 million payment to terminate existing debt. Mustang continues to evaluate opportunities to reduce its cash utilization while focusing on its top priority development programs. Research and development expenses were $40.5 million for the year ended December 31, 2023, compared to $62.5 million for 2022. Non-cash, stock-based compensation expenses included in research and development were $0.1 million for the year ended December 31, 2023, compared to $1.6 million for 2022. Mustang recorded a gain on the sale of property and equipment of $1.5 million, in connection with the sale of assets to uBriGene. General and administrative expenses were $9.7 million for the year ended December 31, 2023, compared to $12.2 million for 2022. Non-cash, stock-based compensation expenses included in general and administrative expenses were $0.4 million for the year ended December 31, 2023, compared to $0.7 million for 2022. Net loss attributable to common stockholders was $51.6 million, or $6.00 per share, for the year ended December 31, 2023, compared to a net loss attributable to common stockholders of $77.5 million, or $10.09 per share, for 2022. 2023 and Recent Corporate Highlights: General Corporate: In July 2023, Mustang announced that it amended its previously announced asset purchase agreement with uBriGene (Boston) Biosciences Inc. (“uBriGene”) and closed the transaction. Per the terms of the amended asset purchase agreement, at closing, uBriGene acquired all of Mustang’s assets primarily relating to the manufacturing and production of cell and gene therapies at Mustang’s manufacturing facility in Worcester, Massachusetts, for upfront consideration of $6 million in cash. An additional $5 million contingent payment will be payable to Mustang upon (i) Mustang raising $10 million in gross proceeds from equity raises following the closing of the transaction and (ii) completion of the assignment of Mustang’s lease to uBriGene, which remains subject to landlord’s approval, within two years of the closing. Unless and until the lease is transferred to uBriGene, Mustang will retain its facility lease and facility personnel and will continue to occupy the leasehold premises and manufacture there its lead product candidate, MB-106. Clearance for assignment of Mustang’s lease to uBriGene remains under review by the U.S. Committee on Foreign Investment in the United States (“CFIUS”), and Mustang and uBriGene are continuing discussions with CFIUS regarding the nature and extent of national security risk posed by the assignment. In October 2023, Mustang completed a registered direct offering priced at-the-market for approximately $4.4 million in gross proceeds. MB-106 (CD20-targeted CAR T-cell therapy): Mustang’s lead clinical candidate is MB-106, a CD20-targeted, autologous CAR T-cell therapy to treat a wide range of hematologic malignancies, including WM and follicular lymphoma (“FL”). MB-106 continues to demonstrate a favorable safety and efficacy pro both the Fred Hutch single institution and Mustang multicenter Phase 1/2 clinical trials. In December 2023, Mustang announced initial data from its ongoing multicenter, open-label, non-randomized Phase 1/2 clinical trial evaluating the safety and efficacy of MB-106 CAR T-cell therapy at the 2023 American Society of Hematology (ASH) Annual Meeting. Initial data show that all patients responded clinically to treatment with MB-106 (n=9), with a 100% overall response rate for patients with FL and WM. 100% of patients with FL (n=5) had a complete response; 1 very good partial response and 2 partial responses were observed in WM patients (n=3); and the hairy cell leukemia variant (“HCL-v”) patient experienced stable disease, with prolonged, ongoing independence from blood transfusions. Complete responses were observed in patients previously treated with CD19-targeted CAR T-cell therapy. MB-106 demonstrated a tolerable safety pro patients with indolent NHL, with no occurrence of cytokine release syndrome (“CRS”) above grade 1, and no immune effector cell-associated neurotoxicity syndrome (“ICANS”) of any grade, despite not using prophylactic tocilizumab or dexamethasone. Outpatient administration was allowed and found to be feasible. MB-106 CAR T-cell expansion and persistence in patients was demonstrated. The FDA granted Orphan Drug Designation to MB-106 for the treatment of WM, and results from this arm of the multicenter trial are expected to support an accelerated Phase 2 registration strategy for WM, with the first pivotal Phase 2 patient with WM to be treated potentially in 2024. Mazyar Shadman, M.D., M.P.H., Study Chair, Associate Professor and physician at Fred Hutch and University of Washington, also presented data from the ongoing Fred Hutch Phase 1/2 clinical trial specific to two B-cell non-Hodgkin lymphoma cohorts, FL and WM. In the FL data cohort (n=20), an overall response rate (“ORR”) of 95% was seen, of which 80% of patients experienced a complete response and 15% had a partial response. The complete response patients include a patient who was previously treated with a CD19-directed CAR T-cell therapy. Of the six patients who experienced cytokine release syndrome (“CRS”), only one had Grade 2, while the remaining five had Grade 1. Ten patients continue to experience complete response for more than 10 months, four patients have experienced complete response for more than two years (all ongoing), and the first patient enrolled has sustained complete response for more than 3 years. In the WM cohort (n=6), all of whom had received prior Bruton tyrosine kinase inhibitor, two patients experienced complete response, one of whom continues to be in complete response at more than 22 months; 1 patient experienced a very good partial response; and 1 patient experienced a partial response. No patients experienced CRS or ICANS greater than Grade 2. None of the six patients with WM has needed to start new therapy for their disease. MB-109 (IL13Rα2-targeted CAR T-cells + HSV-1 oncolytic virus for recurrent glioblastoma): In October 2023, Mustang announced that the FDA accepted the Company’s IND to initiate a Phase 1 open label, multicenter clinical trial to assess the safety, tolerability and efficacy of MB-109, a novel combination of MB-101 (IL13Rα2‐targeted CAR T-cell therapy) and MB-108 (HSV-1 oncolytic virus), for the treatment of recurrent GBM and high-grade astrocytoma. Mustang is evaluating plans to initiate the clinical trial and request orphan drug designation for GBM, subject to resource allocation, in 2024. As previously reported, preclinical data presented at the American Association for Cancer Research (“AACR”) Annual Meeting 2022 supported this combination therapy to optimize results to treat recurrent GBM. The combination leverages MB-108 to make cold tumors “hot,” thereby potentially improving the efficacy of MB-101 CAR T-cell therapy. In March 2024, data from the Phase 1 trial evaluating MB-101 IL13Rα2-targeted CAR T-cells in high-grade glioma were published in Nature Medicine. MB-101 was well tolerated and 50% of patients achieved stable disease or better, with two partial responses and two complete responses in high grade glioma patients. The two patients who achieved complete response both had high levels of intratumoral CD3+ T-cells pre-therapy (i.e., “hot” tumors), and their responses lasted 7.5 and 66+ months, respectively. In the cohort with dual intratumoral (ICT)/ intraventricular (ICV) delivery and an optimized manufacturing process there was a ~70% improvement in median overall survival (10.2 months) compared to the expected survival rate of six months in this patient population. In Vivo CAR-T Technology Platform: Mustang continues to collaborate with the Mayo Clinic to progress our exclusively licensed novel in vivo CAR-T technology platform that may be able to transform the administration of CAR-T therapies and has the potential to be used as an off-the-shelf therapy. Mustang anticipates the publication of proof-of-concept research in a murine tumor model in 2024. MB-117 and MB-217 Lentiviral Gene Therapies for X-Linked Severe Combined Immunodeficiency (XSCID): In 2024, the first patients are expected to be treated in both new investigator-sponsored trials for newborns diagnosed with XSCID and for previously transplanted patients with XSCID. These trials with MB-117 and MB-217, respectively, are planned by our partners and will test a modified version of the current lentiviral vector. About Mustang Bio Mustang Bio, Inc. is a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for difficult-to-treat cancers and rare genetic diseases. Mustang aims to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest, to fund research and development, and to outlicense or bring the technologies to market. Mustang has partnered with top medical institutions to advance the development of CAR-T therapies across multiple cancers, as well as lentiviral gene therapies for severe combined immunodeficiency. Mustang’s common stock is registered under the Securities Exchange Act of 1934, as amended, and Mustang files periodic reports with the U.S. Securities and Exchange Commission (“SEC”). Mustang was founded by Fortress Biotech, Inc. (Nasdaq: FBIO). For more information, visit Forward‐Looking Statements This press release contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Such statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “look forward to,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions. These forward-looking statements, include, but are not limited to, any statements relating to our growth strategy and product development programs, including the timing of and our ability to make regulatory filings such as INDs and other applications and to obtain regulatory approvals for our product candidates, statements concerning the potential of therapies and product candidates and any other statements that are not historical facts. Actual events or results may differ materially from those described in this press release due to a number of risks and uncertainties. Risks and uncertainties include, among other things, risks related to the satisfaction of the conditions necessary to transfer the lease of Mustang’s manufacturing facility and receive the contingent payment in connection with Mustang’s sale of its manufacturing facility in the anticipated timeframe or at all; whether the purchaser of Mustang’s manufacturing facility is able to successfully perform its obligation to produce Mustang’s products under the manufacturing services agreement on a timely basis and to acceptable standards; disruption from the sale of Mustang’s manufacturing facility making it more difficult to maintain business and operational relationships; negative effects of the announcement or the consummation of the transaction on the market price of Mustang’s common stock; significant transaction costs; the development stage of Mustang’s primary product candidates, our ability to obtain, perform under, and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third-party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in Part I, Item 1A, “Risk Factors,” in our Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q, and our other filings we make with the SEC. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by applicable law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Company Contacts: Jaclyn Jaffe and Nicole McCloskey Mustang Bio, Inc. (781) 652-4500 ir@mustangbio.com MUSTANG BIO, INC. Balance Sheets (in thousands, except for share and per share amounts) December 31, December 31, 2023 2022 ASSETS Current Assets: Cash and cash equivalents $ 6,234 $ 75,656 Other receivables - related party - 36 Other receivables 3,879 263 Prepaid expenses and other current assets 1,233 2,897 Total current assets 11,346 78,852 Property, plant and equipment, net 3,218 8,440 Fixed assets - construction in process 29 951 Restricted cash 750 1,000 Other assets 833 261 Operating lease right-of-use asset, net 1,566 2,918 Total Assets $ 17,742 $ 92,422 LIABILITIES AND STOCKHOLDERS’ EQUITY Current Liabilities: Accounts payable and accrued expenses $ 14,017 $ 13,731 Payables and accrued expenses - related party 834 766 Operating lease liabilities - short-term 520 612 Total current liabilities 15,371 15,109 Deferred income 270 270 Note payable, long-term, net - 27,436 Operating lease liabilities - long-term 1,978 3,334 Total Liabilities 17,619 46,149 Stockholders’ Equity Preferred stock ($0.0001 par value), 2,000,000 shares authorized, 250,000 shares of Class A preferred stock issued and outstanding as of December 31, 2023 and 2022, respectively — — Common stock ($0.0001 par value), 200,000,000 shares authorized as of December 31, 2023 and 2022, respectively Class A common shares, 845,385 shares issued and outstanding as of December 31, 2023 and 2022, respectively — — Common shares, 8,374,869 and 7,100,111 shares issued and outstanding as of December 31, 2023 and 2022, respectively 1 11 Common stock issuable, 419,089 and 187,134 shares as of December 31, 2023 and 2022, respectively 591 1,109 Additional paid-in capital 380,502 374,522 Accumulated deficit (380,971 ) (329,369 ) Total Stockholders’ Equity 123 46,273 Total Liabilities and Stockholders’ Equity $ 17,742 $ 92,422 MUSTANG BIO, INC. Statements of Operations (in thousands, except for share and per share amounts) For the year ended December 31, 2023 2022 Operating expenses: Research and development $ 40,513 $ 62,475 Research and development – licenses acquired 527 1,474 Gain on the sale of property and equipment (1,466 ) — General and administrative 9,686 12,210 Total operating expenses 49,260 76,159 Loss from operations (49,260 ) (76,159 ) Other income (expense) Other income 917 1,304 Interest income 850 689 Interest expense (4,109 ) (3,359 ) Total other income (expense) (2,342 ) (1,366 ) Net Loss $ (51,602 ) $ (77,525 ) Net loss per common share outstanding, basic and diluted $ (6.00 ) $ (10.09 ) Weighted average number of common shares outstanding, basic and diluted 8,604,104 7,684,508

A BeiGene drug already used to treat several types of blood cancer now has an additional FDA approval as a treatment for follicular lymphoma. The regulatory decision makes the BeiGene drug the first in its class for treating this type of cancer. The FDA last Thursday approved zanubrutinib, brand name Brukinsa, for patients whose follicular lymphoma has not responded to two or more lines of therapy. BeiGene’s twice-daily capsule is administered alongside periodic infusions of obinutuzumab, brand name Gazyva, a targeted therapy from Roche that is a standard follicular lymphoma treatment. The new approval comes four months after European Commission approval of Brukinsa for follicular lymphoma. Follicular lymphoma is a slow-growing form of non-Hodgkin lymphoma, a cancer affecting white blood cells called lymphocytes. Brukinsa belongs to a class of therapies called BTK inhibitors. The small molecule drug is designed to block Bruton’s tyrosine kinase (BTK), an enzyme that drives cancer cell growth. The approval in follicular lymphoma is based on the results of a clinical trial that enrolled 217 adults and compared treatment with Brukinsa and Gazyva to treatment with Gazyva alone. The main goal was to measure the overall response rate and the duration of response. Results showed an overall response rate of 68% in the study drug arm compared to 46% in the control group. With a median follow-up of 19 months, the median duration of response was not reached in the Brukinsa/Gazyva arm, and was 14 months in the Gazyva group. Across the drug’s clinical trials, the most common adverse reactions included low levels of a type of white blood cell called a neutrophil, upper respiratory tract infections, bleeding, and muscle pain. Brukinsa won its first FDA approval in 2019 for the treatment of mantle cell lymphoma. Its other approved indications are Waldenstrom’s macroglobulinemia, marginal zone lymphoma, and chronic lymphocytic leukemia (CLL). The drug is BeiGene’s top product, accounting for $1.3 billion in revenue in 2023, a more than 128% increase over the product’s sales in 2022. In its annual report, BeiGene said Brukinsa’s U.S. sales growth in 2023 was driven by the product’s launch in CLL. Brukinsa is currently approved in 70 countries. With Brukinsa’s latest FDA nod, the BTK inhibitor joins a small group of therapies already available as third-line treatments for follicular lymphoma. The CAR T-therapies Kymriah from Novartis and Yescarta from Gilead Sciences are such treatment options. Another choice is Lunsumio, a bispecific T cell engager developed by Roche and approved by the FDA in 2022. The FDA nod for Brukinsa in follicular lymphoma is an accelerated approval that requires a post-marketing study to confirm the therapy’s efficacy. BeiGene said a Phase 3 trial already underway will serve as the confirmatory clinical trial for this indication. “This accelerated approval of Brukinsa represents an important advancement, offering the first and only BTK inhibitor treatment for follicular lymphoma patients in the U.S. who have either not responded to initial therapies or have experienced relapse,” Mehrdad Mobasher, BeiGene’s chief medical officer, hematology, said in a prepared statement. Here’s a recap of other recent regulatory news: —Blockbuster Novo Nordisk drug Wegovy, approved as a treatment for weight management, is expanding its label to include reducing cardiovascular risks in those who are obese or overweight. FDA approval of the additional indication is based on results from a clinical trial showing that patients who treated with Wegovy experienced a significantly lower rate of cardiovascular events compared to those who received a placebo. That study followed more than 17,000 participants for up to five years. —Eli Lilly Alzheimer’s disease drug donanemab won’t receive a first quarter 2024 regulatory decision as expected. The FDA wants to convene an advisory panel to discuss the safety and efficacy of the antibody drug, including the unique trial design that allowed patients to complete their course of treatment upon reaching a prespecified level of amyloid plaque clearance. The meeting date has not yet been set. Lilly said holding an advisory committee for donanemab is consistent with the review of Aduhelm and Leqembi, antibody drugs that previously won approvals in Alzheimer’s disease. —Sandoz received FDA approvals for two biosimilars that are interchangeable with the blockbuster Amgen products Prolia and Xgeva, antibody drugs that block a protein called RANKL to treat osteoporosis and bone problems in cancer patients. The new Sandoz drugs, Jubbonti and Wyost, are the first FDA-approved RANKL inhibitor biosimilars. —Partners Formosa Pharmaceuticals and Aimax Therapeutics received FDA approval for a new formulation of a topical steroid developed for treating inflammation and pain following eye surgery. The drug, clobetasol propionate ophthalmic suspension, is made with Formosa’s nanoparticle formulation technology. The Formosa drug will be commercialized in the U.S. by Eyenovia, a New York company that acquired U.S. rights to the steroid. A mid-year launch is planned. Eyenovia also said it also exploring development of this product, delivered with its Optejet dispenser device, as a potential treatment for dry eye disease. —The FDA approved Johnson & Johnson drug Rybrevant as a first-line treatment for non-small cell lung cancer that carries the rare EGFR exon 20 insertion mutation. The J&J antibody drug initially won accelerated approval in 2021. The new FDA decision converts Rybrevant’s status to full approval. It’s based on the results of a confirmatory Phase 3 study that showed a statistically significant improvement in progression-free survival. —EMD Serono, the healthcare business of German company Merck KGaA, also converted an accelerated approval to a traditional one. The FDA approved the company’s Tepmetko for treating adults with advanced non-small cell lung cancer that has MET exon 14 skipping alterations. Tepmetko received accelerated FDA approval in 2021. —The FDA turned down a Minerva Neurosciences application seeking approval of roluperidone as a treatment for symptoms of schizophrenia. The drug is designed to selectively block certain receptors involved in regulating brain functions, such as mood and anxiety. Among the deficiencies cited: The application included a statistical significance finding from only one clinical trial, which on its own is insufficient to provide substantial evidence of effectiveness, the agency told Minerva. The FDA asked Burlington, Massachusetts-based Minerva to submit data from at least one additional well-controlled clinical trial and also provide more data to show the drug’s safety and efficacy when co-administered with other antipsychotic medications. Minerva said it would request a meeting to discuss the FDA letter. —Allecra Therapeutics received FDA approval for Exblifep for treating complicated urinary tract infections in adults. The antibiotic is part of a class of drugs that work by inhibiting synthesis of a bacterium’s cell wall. With the approval, France and Germany-based Allecra receives five-year marketing exclusivity for the product under the Generating Antibiotic Incentives Now Act, which was enacted to incentivize anti-infective product R&D. Allecra said it is in discussions with potential U.S. commercialization partners for Exblifep. —Novartis is withdrawing Adakveo from the U.K. market after post-marketing testing failed to confirm the drug’s benefit. Adakveo was developed to treat vaso-occlusive crises, a complication of sickle cell disease. The exit from the U.K. market follows the withdrawal of the drug from the European Union last year. At that time, the company said it also planned to discuss the study results with the FDA. —The European Commission granted marketing authorization for Pfizer drug Velsipity as a treatment for moderately to severely active ulcerative colitis in patients 16 and older. The once-daily oral drug is a small molecule designed to selectively target and block three S1P receptors. European approval of Velsipity follows the drug’s FDA approval last October. —Iovance Biotherapeutics’ Amtagvi won the first FDA approval for a type of cell therapy called a tumor-infiltrating lymphocyte, or TIL. The regulatory decision also marks the first approval of a cell therapy for treating solid tumors. Amtavi’s approval specifically covers the treatment of advanced cases of melanoma. The one-time treatment carries a $515,000 wholesale price. —Xolair, an old Roche drug whose approved uses include treating asthma, received a new FDA approval for reducing allergic reactions in people who have food allergies. Xolair is an antibody that blocks immunoglobulin E, an antibody produced by the immune system in response to an allergen. The drug’s latest regulatory decision covers adults as well as children age 1 and older who have food allergies. Xolair’s is not an emergency treatment for allergic reactions to food. People who have food allergies should continue to avoid trigger foods. But Xolair reduces allergic reactions in instances of accidental exposure to a food allergen.

Pictured: FDA sign outside its office in Maryland/iStock, hapabapa The FDA on Thursday granted accelerated approval to BeiGene’s BTK inhibitor Brukinsa (zanubrutinib), when used in combination with Genentech’s Gazyva (obinutuzumab), to treat patients with relapsed or refractory follicular lymphoma who have undergone at least two lines of systemic therapy. The regulatory win makes Brukinsa the first and only BTK inhibitor authorized for use in follicular lymphoma (FL) and the first therapy in this drug class to secure five oncology indications, according to BeiGene’s announcement. Brukinsa “is the only BTK inhibitor to date that shows efficacy with this type of malignancy and now has the broadest label,” BeiGene CMO Mehrdad Mobasher said in a statement, adding that Thursday’s approval is a “testament to Brukinsa’s differentiate clinical profile.” The FDA’s decision was backed by data from the Phase II ROSEWOOD trial, a randomized and open-label study that demonstrated a 69% overall response rate (ORR) in patients treated with Brukinsa plus Gazyva. Those who received Gazyva alone had an ORR of 46%. The treatment difference was statistically significant in favor of Brukinsa, with a p-value of 0.0012, according to BeiGene. At 18 months, ROSEWOOD documented a “landmark” duration of response rate of 69% in the combination treatment arm. In terms of safety, the trial found that Brukinsa plus Gazyva was overall well-tolerated, with a safety pro with what had been previously established for both treatments. Of the patients who received the combination regimen, 35% developed serious adverse events and 17% discontinued Brukinsa permanently due to toxicities. Brukinsa’s FL approval was given under the FDA’s accelerated pathway, which requires BeiGene to run a confirmatory trial to verify Brukinsa’s clinical benefits in this indication. The biotech is conducting the Phase III MAHOGANY trial, which is currently underway. Brukinsa is a small molecule blocker of the Bruton’s tyrosine kinase protein, which is involved in signaling pathways that culminate in B-cell proliferation, trafficking, adhesion and movement. This mechanism of action allows Brukinsa to inhibit and suppress the proliferation of malignant B-cells and limit tumor growth. The drug was first approved in November 2019 for the treatment of mantle cell lymphoma in adult patients who had undergone at least one previous line of therapy. Brukinsa has since picked up other indications including relapsed or refractory marginal zone lymphoma, marginal zone lymphoma, chronic lymphocytic lymphoma and the blood cell cancer Waldenström’s macroglobulinemia. BeiGene’s regulatory victory on Thursday comes nearly a year after AbbVie and J&J voluntarily withdrew two accelerated approvals for Imbruvica (ibrutinib), one of Brukinsa’s primary competitors. Following disappointing data from Phase III confirmatory trials, the pharma partners pulled Imbruvica’s indications in mantle cell lymphoma and marginal zone lymphoma. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.