On November 14, 2023 Biohaven Ltd. (NYSE: BHVN) (Biohaven or the Company), a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies to treat a broad range of rare and common diseases, reported financial results for the third quarter ended September 30, 2023, and provided a review of recent accomplishments and anticipated upcoming milestones (Press release, Biohaven Pharmaceutical, NOV 14, 2023, View Source [SID1234637666]).

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Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven, commented, "Our team at Biohaven continued to make tremendous progress this past quarter in advancing multiple development programs and innovating across our entire pipeline. Most recently, we shared important data from our molecular degrader of extracellular proteins (MoDE) program and demonstrated the potential for this technology in the field of immunology where targeting pathologic antibodies has been shown to have important therapeutic potential. We have demonstrated that BHV-1300, our lead IgG degrader, has great potential with a differentiated profile including: rapid onset of action, deeper reductions in IgG levels compared to FcRN targeting agents, lack of anticipated mechanistic effects on albumin or cholesterol, potential for self-administered subcutaneous dosing, and the compatibility to dose in combination with standard of care biologic therapeutic agents. BHV-1300 offers a highly competitive mechanism of action and potential for favorable differentiation from FcRn targeting agents. In addition, our technology can be readily modified to expand therapeutic targets past IgG to include other immunoglobulins (IgA, IgM, IgE, etc) and antigen specific autoantibodies. With multiple opportunities to address rare and common diseases alike, we continue to be impressed by the expansive potential of our degrader program.

Beyond our extracellular degraders, we also shared key data from ongoing studies with BHV-7000, our highly selective Kv7.2/7.3 activator for epilepsy, mood disorders and pain. Consistent with results observed in clinical and non-clinical studies, EEG data reported last month confirmed CNS target engagement without showing waveform increases in frequencies typically associated with adverse events commonly associated with existing ASMs, such as somnolence and other CNS effects; we expect to present additional details and analyses from this EEG study at an upcoming scientific meeting soon. With target engagement now confirmed in EEG biomarker studies, a favorable safety profile demonstrated in Phase 1 studies, and development of a once-daily formulation of BHV-7000 complete, we look forward to initiating our Phase 3 program in focal epilepsy, which we expect to commence before the end of 2023 — a program poised to offer paradigm shifting potential in preventing seizures without burdensome CNS side effects. Separately, we completed enrollment in RESILIENT, our Phase 3 pivotal study of taldefgrobep alfa in SMA in record time, thanks to our partnership with the global SMA community and the remarkably efficient clinical trial expertise that we have in-house at Biohaven."

Dr. Coric continued, "With the closing of our recent public offering and achievement of several important milestones across our programs, we are in a strong position with access to approximately $495 million in capital following our public offering this month to continue to invest in accelerating and executing on our innovative pipeline. Our unwavering patient focus and methodical scientific approach drives every layer of our decision making, and we will progress and phase programs to balance our commitment with prudent resource allocation."

Third Quarter 2023 and Recent Business Highlights

Reported on continued progress with first-in-class bispecific IgG degrader, BHV-1300, as compound advances to IND submission by the end of 2023 – In September 2023, the Company announced preliminary analyses and positive pharmacodynamic data from a preclinical study evaluating BHV-1300 in cynomolgus monkeys. Repeat dosing of BHV-1300 produced dose-dependent reductions of over 90% in IgG levels from baseline, suggesting the potential for achieving greater efficacy with finely calibrated, deeper IgG reductions as compared with existing standard of care FcRn targeting treatments. The Company remains on track to submit an IND application for BHV-1300 in 2023; the Company also expects to submit an IND application for its first-in-class bispecific IgA degrader BHV-1400 in the second half of 2024.
Public offering – On October 5, 2023, the Company closed its previously announced underwritten public offering of 11,761,363 of its common shares, which included the full exercise of the underwriters’ option to purchase 1,534,090 additional shares, at the public offering price of $22.00 per share. The net proceeds raised in the offering, after deducting underwriting discounts and estimated expenses of the offering payable by the Company, were approximately $242.4 million. As of November 10, 2023, we had 80,233,656 common shares outstanding.
Announced preliminary analyses and positive biomarker data from Biohaven’s exploratory Phase 1 EEG biomarker study and completed once-daily formulation development – In September 2023, the Company announced preliminary analyses and positive biomarker data from its Phase 1 EEG biomarker study confirming CNS activity of BHV-7000 at projected therapeutic concentrations and drug concentration-dependent (i.e., dose-dependent and time-dependent) changes in EEG spectral power consistent with EEG effects observed with other ASMs approved for the treatment of epilepsy. BHV-7000 was well tolerated in the exploratory EEG study and the safety profile was consistent with the previously reported safety data from the Phase 1 SAD/MAD trial completed to date in healthy volunteers. The Company expects to share additional results from this EEG study at the upcoming American Epilepsy Society (AES) medical meeting in December.
Successfully dosed three cohorts with single ascending doses of oral, brain penetrant, dual TYK2/JAK1 agent, BHV-8000 – In July 2023, the Company announced that it successfully dosed three cohorts in the SAD portion of an ongoing SAD/MAD Phase 1 study evaluating brain penetrant TYK2/JAK1 agent, BHV-8000 in healthy volunteers. The ongoing Phase 1 study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of BHV-8000 in healthy volunteers. Based on the preliminary data available, projected therapeutic concentrations of BHV-8000 were achieved, and BHV-8000 was well tolerated with only mild adverse events reported. These data provide support for further development of BHV-8000, and the Company anticipates beginning a Phase 2/3 clinical trial with BHV-8000 in Parkinson’s disease and potentially other neuroinflammatory diseases in 2024.
Presented preclinical data demonstrating taldefgrobep alfa reduces fat and improves lean mass at ObesityWeek – In October 2023, the Company announced the presentation of preclinical data demonstrating the ability of taldefgrobep alfa to significantly reduce fat mass while increasing lean mass in an obese mouse model at The Obesity Society’s annual ObesityWeek conference. Separately, the Company reported data supporting the correlation between change in waist circumference and change in total body weight among adults living with overweight and obesity treated with approved anti-obesity medications.
Completed enrollment in pivotal Phase 3 study of taldefgrobep alfa in SMA – In September 2023, the Company announced that it had completed enrollment in RESILIENT, a pivotal Phase 3 study designed to evaluate the efficacy and safety of taldefgrobep as adjunctive therapy to enhance muscle mass and function in SMA patients treated with standard-of-care treatments. Taldefgrobep is the only myostatin inhibitor in clinical development that targets both myostatin and activin A signaling, two key regulators of muscle mass. In July 2023, the Company announced that taldefgrobep received ODD from the European Commission for the treatment of SMA. Taldefgrobep previously received Fast-Track and ODD from the FDA.
Expected Upcoming Milestones:

Biohaven is progressing its product candidates through clinical programs in a number of common and rare disorders. The Company expects to reach significant pipeline milestones in the coming periods. Biohaven expects to:

Announce additional Phase 1 EEG study results for Kv7 activator BHV-7000 at the American Epilepsy Society Annual Meeting in December: The Company expects to present complete results from its EEG study with BHV-7000 in healthy volunteers by the end of the year.
Initiate Phase 3 programs with BHV-7000 in the second half of 2023 and first half of 2024: Biohaven expects to initiate pivotal trials in patients with focal epilepsy by the end of 2023 and bipolar disorder in the first half of 2024.
Submit IND with BHV-1300, the Company’s lead extracellular degrader: The Company expects to advance our IND for the lead IgG degrader BHV-1300 by year-end 2023.
Submit IND with selective Gd-IgA1 degrader BHV-1400: The Company expects to submit an IND with Gd-IgA1 degrader BHV-1400, indicated for IgA nephropathy, in the second half of 2024.
Initiate Phase 2/3 study with brain penetrant, dual TYK2/JAK1 inhibitor BHV-8000 in Parkinson’s disease: The Company commenced Phase 1 studies with BHV-8000, an oral, brain-penetrant, dual TYK2/JAK1 inhibitor for neuroinflammatory disorders, in the first half of 2023 and expects to initiate a Phase 2/3 study in Parkinson’s disease in 2024.
Submit IND with TRPM3 antagonist BHV-2100: The Company expects to submit an IND with BHV-2100, a selective TRPM3 antagonist in the Company’s ion channel platform, indicated for pain disorders, including migraine, by year-end 2023.
Taldefgrobep alfa program updates: The Company expects to initiate a Phase 2 trial in metabolic disorders in 2024.
Complete enrollment in Phase 3 studies of troriluzole in OCD in 2024: Two Phase 3 randomized, double-blind, placebo-controlled studies of troriluzole in OCD are expected to enroll up to 700 patients (in each trial) across nearly 200 global study sites. The Company anticipates completing enrollment in the Phase 3 trials in 2024.
Continue advancements across multiple neuroscience and immunoscience indications: The Company’s preclinical pipeline includes a platform of bispecific degraders of extracellular proteins directed against IgG, IgA and other targets, TRPM3 and Kv7 family of ion channel modulators, and other undisclosed targets.
Capital Position:

Cash, cash equivalents, marketable securities and restricted cash totaled approximately $495 million as of October 5, 2023, which included net proceeds of $242 million from completed public offering on October 5, 2023.

Third Quarter 2023 Financial Highlights:

Research and Development (R&D) Expenses: R&D expenses, including non-cash share-based compensation costs, were $95.5 million for the three months ended September 30, 2023, compared to $52.8 million for the three months ended September 30, 2022. The increase of $42.7 million was primarily due to increases in direct program spend for additional and advancing clinical trials, including late Phase 2/3 studies, and preclinical research programs in 2023, as compared to the same period in the prior year. Non-cash share-based compensation expense was $2.2 million for the three months ended September 30, 2023, a decrease of $7.5 million as compared to the same period in 2022. Non-cash share-based compensation expense was higher in the third quarter of 2022 primarily because expense allocated from Biohaven Pharmaceutical Holding Company Ltd.’s (the Former Parent[1]) equity plan, prior to the spin-off, was based on equity awards with higher grant date fair values, which was partially offset by increased personnel costs related to increased headcount in 2023.

General and Administrative (G&A) Expenses: General and administrative expenses were $15.0 million for the three months ended September 30, 2023, compared to $14.8 million for the three months ended September 30, 2022. The increase of $0.2 million was increased personnel costs in the third quarter of 2023 due to a majority of the personnel costs in three months ended September 30, 2022 being allocated to the Former Parent, offset by decreased non-cash share-based compensation costs. Non-cash share-based compensation expense was $2.3 million for the three months ended September 30, 2023, a decrease of $5.0 million as compared to the same period in 2022. Non-cash share-based compensation expense was higher in the third quarter of 2022 primarily because expense allocated from the Former Parent equity plan, prior to the spin-off, was based on equity awards with higher grant date fair values.

Other Income (Expense), Net: Other income (expense), net was a net income of $4.7 million for the three months ended September 30, 2023. The Company did not record any other income (expense) for the three months ended September 30, 2022. The increase of $4.7 million was primarily due to an increase in net investment income of $3.8 million and an increase of $1.2 million in other income related to our transition services provided to the Former Parent, which is largely non-recurring.

Net Loss: Biohaven reported a net loss for the three months ended September 30, 2023, of $102.6 million, or $1.50 per share, compared to $68.9 million, or $1.75 per share, for the same period in 2022. Non-GAAP adjusted net loss for the three months ended September 30, 2023 was $98.1 million, or $1.44 per share, compared to $49.2 million, or $1.25 per share for the same period in 2022. These non-GAAP adjusted net loss and non-GAAP adjusted net loss per share measures, more fully described below under "Non-GAAP Financial Measures," exclude non-cash share-based compensation charges. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the tables below. For periods prior to the Spin-Off, net loss per share and non-GAAP adjusted net loss per share were calculated based on the 39,375,944 common shares of Biohaven distributed to the Former Parent shareholders at the time of the distribution, including common shares issued in connection with the Former Parent share options that were settled on October 3, 2022 and common shares issued in connection with the Former Parent restricted share units that vested on October 3, 2022. The same number of shares is being utilized for the calculation of basic and diluted earnings per share for all periods presented prior to the Spin-Off.

On November 14, 2023 JelloX Biotech Inc., a Taiwan-based startup focused on cancer pathology, reported new research and conference milestones, coinciding with its 5th anniversary in November 2023 (Press release, JelloX Biotech, NOV 14, 2023, View Source [SID1234637665]). With significant parts of the medical field starting to leverage AI for pharmaceutical R&D and patient risk assessment, JelloX continues to distinguish itself as an early adopter of AI applied to cancer pathology.

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Advancing immunotherapy at ESMO (Free ESMO Whitepaper) Congress 2023

An influential conference in the European oncology space, ESMO (Free ESMO Whitepaper) Congress 2023 took place from October 20 to 24 and featured significant dialogue around the latest advancements in immunotherapy (IO), antibody-drug conjugates (ADCs), and AI. Invited to present, JelloX’s unique application of AI in 3D pathology for cancer drew significant interest from attendees, and its latest research demonstrated new possibilities for biomarker-based patient screening prior to IO treatments.

Specifically, its new findings focused on breast cancer and PD-L1 biomarker, a key diagnostic target for immunotherapy:

The study showed that AI analysis of 3D images was able to identify an additional 30% of patients with tumor heterogeneity that traditional 2D methods missed, necessitating more precise immunotherapy treatments.
Findings reinforced that AI analysis of 3D images allows for a more comprehensive understanding of tumor complexity and heterogeneity, thereby facilitating more accurate treatment.
A new AI algorithm introduced for the study demonstrated that AI is also a powerful tool for analyzing digitalized traditional (2D) sample imaging by reducing processing times.
AI at 2023 TAITA-SV Annual Conference

The Silicon Valley Taiwanese-American Industrial Technology Association (TAITA-SV) held its Annual Conference on October 7, where Dr. Yen-Yin Lin, CEO of JelloX, was featured as the only Taiwan-based speaker on the Bio panel. Dr. Lin shared insights on the role of AI in medicine and healthcare, particularly how JelloX is leveraging this technology — along with 3D imaging — to advance cancer pathology diagnosis and precision treatment.

"We estimate that 40% of cancer patients can benefit from AI-analyzed 3D pathology, especially those undergoing immunotherapy," noted Dr. Lin. "Leveraging AI to analyze 3D tumor imaging has great potential to disrupt oncology, through offering a more efficient and precise approach to treatment."

JelloX’s 3D pathology addresses the low sampling rate issue common in cancer biopsies, offering a more comprehensive evaluation of a tumor’s many biomarkers.

He continued: "When it comes to cancer diagnosis and treatment, precision is paramount and efficiency is everything. Our solutions are critical to matching the right patients to the right drugs and to identifying suitable candidates for pharmaceutical research."

Dr. Lin also highlighted the growing importance of cloud and edge devices in the future of pathology, emphasizing their roles in enabling mobile and remote usage. He shared further how JelloX is collaborating with technology firms to analyze and leverage big data, working towards a federated learning model that can be shared by oncologists worldwide — creating a collaborative, informed global community united in the fight against cancer.

On November 14, 2023 CASI Pharmaceuticals, Inc. (Nasdaq: CASI), a biopharmaceutical company focused on developing and commercializing innovative therapeutics and pharmaceutical products, reported business and financial results for the third quarter ended September 30, 2023 (Press release, CASI Pharmaceuticals, NOV 14, 2023, View Source [SID1234637664]).

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Dr. Wei-Wu He, Chairman and CEO of CASI Pharmaceuticals, stated, "We are delighted to announce that our partner Juventas has received approval from the China National Medical Products Administration (NMPA) for Inaticabtagene Autoleucel (anti-CD 19 CAR-T Cell Therapy) for the treatment of B-cell acute lymphoblastic leukemia (r/r B-ALL) in China. As exclusive marketing partner of Juventas, we are extremely proud of this achievement. This marks a significant milestone as Inaticabtagene Autoleucel is the first commercialized cell therapy for B-ALL in China. Our sales and marketing team is actively preparing for the commercial launch."

Dr. He further added, "Our sales revenue for the third quarter of 2023 was $8.8 million, representing a decrease of 13.5% compared to the same period last year and a decrease of 10% from the second quarter of 2023. The third quarter EVOMELA sales performance was impacted by the recent launch of an undifferentiated generic formulation of melphalan for injection product. Despite market challenges, CASI remains committed to advancing our product pipeline. Some of our noteworthy recent achievements include the license transfer of Folotyn with an expected launch in Q1 2024, progress in the clinical development of BI-1206, transitioning CID-103 development to China for malignant hematology indications, and the acquisition of global rights for CB-5339 from Cleave Therapeutics. CASI Pharmaceuticals continues to strive for milestones and seek new synergistic opportunities in the coming quarters."

Third Quarter 2023 Financial Highlights

Revenue consists of product sales of EVOMELA. Revenue was $8.8 million for the three months ended September 30, 2023, compared to $10.2 million for the three months ended September 30, 2022.
Costs of revenues were $3.6 million for the three months ended September 30, 2023, compared to $4.2 million for the three months ended September 30, 2022. The decrease is in line with the decrease in revenue.
Research and development expenses for the three months ended September 30, 2023 were $2.4 million, compared with $3.9 million for the three months ended September 30, 2022. The decrease is mainly attributable to reduced research and development expenses on certain projects, such as CID-103.
General and administrative expenses for the three months ended September 30, 2023 were $5.5 million, compared with $4.8 million for the three months ended September 30, 2022.
Selling and marketing expenses for the three months ended September 30, 2023 were $2.5 million, compared with $3.6 million for the three months ended September 30, 2022. The decrease is mainly attributable to reduced commercial activities given the recent market environment.
As of September 30, 2023, CASI had cash, cash equivalents and short-term investments of $34.2 million.

On November 14, 2023 Aptevo Therapeutics Inc. (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immune-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported financial results for the quarter ended September 30, 2023 and provided a business update (Press release, Aptevo Therapeutics, NOV 14, 2023, View Source [SID1234637662]).

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Business Highlights

On August 4, 2023, Aptevo closed a public offering for $5 million that included healthcare-focused institutional investors. The Company raised an additional $2 million through the exercise of warrants in November 2023. This funding extends cash runway for at least the next twelve months
The Company may also receive up to $9.2 million if additional warrants are exercised
The ALG.APV-527 Phase 1 dose escalation trial for the treatment of multiple solid tum 5T4 continues to dose patients and progress in the clinic
Trial endpoints include identification of an expansion phase dose and signals of clinical activity
Planning for initiation of the Company’s Phase 2 program evaluating APVO436 in two clinical trials (relapsed/refractory and frontline AML) is ongoing
The Phase 2 program is intended to further evaluate the triplet combination of APVO436 + venetoclax + azacitidine among frontline and relapsed/refractory AML patients who are venetoclax treatment naïve
" Our work in the third quarter demonstrates Aptevo’s continued commitment to making progress across the pipeline with the goal of helping people in the fight against cancer and we are making strides. We remain on track with the execution of our Phase 1 dose escalation trial evaluating ALG.APV-527 for multiple solid tumors. We are excited about 527 because of its potential for broad applicability in solid tumors expressing 5T4 and the emerging therapeutic promise of the 4-1BB pathway," said Marvin White , President and Chief Executive Officer at Aptevo. "We also raised a total of $7 million through an equity raise and the exercise of warrants. This funding extends cash runway well into 4Q24 when we will reach impactful clinical milestones."

"We are extremely pleased with our APVO436 AML data which demonstrate the safety, clinical activity and durability of the treatment effect," said Dirk Huebner, MD, Chief Medical Officer at Aptevo. "Importantly, we also learned that the drug can be safely administered together with an established standard of care without significantly adding to the toxicity burden for the patient. The data show that APVO436 is combinable with chemotherapy, and we are particularly interested in the combination of APVO436 with venetoclax and azacitidine."

Third Quarter 2023 Financial Results

Cash Position: Aptevo had cash and cash equivalents as of September 30, 2023 totaling $19.1 million.

Royalty Revenue: Royalty revenue for the period covered by this report reflects revenue recorded only in the first quarter of 2022 due to our Amendment to Royalty Purchase Agreement with HCR. As a result of the amendment, we ceased reporting as royalty revenue, royalties paid by Pfizer to HCR related to Pfizer’s sales of RUXIENCE (rituximab-pvvr). The last quarter for which we reported this royalty revenue was Q1 2022. The Amendment had the effect of eliminating the requirement to report all future Pfizer non-cash royalty revenue and extinguishing the liability that we recorded upon the initial sale of the royalties to HCR. RUXIENCE is a registered trademark of Pfizer.

Research and Development Expenses : Research and development expenses decreased by $0.6 million, from $4.5 million for three months ended September 30, 2022 to $3.9 million for the three months ended September 30, 2023. The decrease was primarily due to lower spending on the APVO436 Phase 1b clinical trial as we concluded enrollment in that study and lower spending on preclinical projects and employee costs. The decrease is partially offset by higher spending on the ALG.APV-527 Phase 1 clinical trial as we continue to enroll new patients and sites.

General and Administrative Expenses : General and administrative expenses decreased by $0.6 million, from $3.3 million for the three months ended September 30, 2022 to $2.7 million for the three months ended September 30, 2023. The decrease is primarily due to lower employee and consulting costs.

Other Income (Expense) Net: Other income (expense), net consists primarily of a gain related to the sale of a nonfinancial asset, costs related to debt extinguishment, accrued exit fees on debt, non-cash interest on financing agreements, and interest on debt. Other income, net was $0.2 million for the three months ended September 30, 2023. Other expense, net was $0.1 million for the three months ended September 30, 2022. The change in other income (expense), net is primarily due to higher interest income from our money market funds and not having interest expense related to our MidCap term loan during the quarter due to full repayment of the outstanding balance in the first quarter of 2023.

Discontinued Operations: We did not have income from discontinued operations for the three months ended September 30, 2023. As a result of our Purchase Agreement with XOMA (US) LLC in March 2023, we no longer receive deferred payments from Medexus. We are still entitled to receive a percentage of future milestones based on Medexus’ achievement of certain IXINITY net sales and regulatory approvals. Income from discontinued operations was $0.2 million for the three months ended September 30, 2022, which related to collection of deferred payments from Medexus related to IXINITY sales.

Net Income (Loss) : Aptevo had a net loss of $6.3 million or $0.50 per share for the three months ended September 30, 2023, compared to a net loss of $7.6 million or $1.50 per share for the corresponding period in 2022.

On November 14, 2023 Mustang Bio, Inc. ("Mustang") (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, reported financial results and recent corporate highlights for the third quarter that ended September 30, 2023 (Press release, Mustang Bio, NOV 14, 2023, View Source [SID1234637661]).

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Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "In the third quarter of 2023, Mustang continued to make meaningful progress in the development of our lead clinical candidate MB-106, a CD20-targeted, autologous CAR-T cell therapy to treat relapsed or refractory B-cell non-Hodgkin lymphomas ("B-NHL") and chronic lymphocytic leukemia ("CLL"). We announced the first data from our ongoing multicenter, open-label, non-randomized Phase 1/2 clinical trial evaluating MB-106’s safety and efficacy. The data were consistent with efficacy and safety results from the ongoing investigator-sponsored trial at Fred Hutchinson Cancer Center ("Fred Hutch") which have shown complete remission for as long as three years. In the multicenter trial, substantial clinical benefit was observed in all four indolent lymphoma patients treated at dose level 1 (3.3 x 106 cells/kg), including two complete responses in follicular lymphoma ("FL") patients, one of whom was previously treated with CD19 CAR-T cell therapy. A third patient, with a diagnosis of Waldenstrom macroglobulinemia ("WM"), who had nine prior treatments and high disease burden, achieved a very good partial response, which is generally the best response that can be achieved in this disease. No cytokine release syndrome greater than Grade 1 was observed in any of the four patients, and no occurrences of immune effector cell-associated neurotoxicity syndrome were reported. Additional safety and efficacy data from the multicenter trial will be reported at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") Annual Meeting in December, including follow-up for the four dose-level-1 patients and data from all patients treated at dose level 2 (1.0 x 107 cells/kg) who have had at least 28 days of follow-up. At the End-of-Phase 1 meeting with the FDA expected in the first quarter of 2024, Mustang anticipates recommending dose level 2 as the Phase 2 dose for indolent lymphoma. Mustang further anticipates that results from the Phase 1 indolent lymphoma arm of the multicenter trial will support an accelerated Phase 2 registration strategy for WM, with the first pivotal Phase 2 WM patient to be treated potentially in mid-2024. Additionally, we plan to initiate a pivotal Phase 2 clinical trial in at least one additional B-cell malignancy in 2025."

Dr. Litchman continued, "Mustang also announced that the U.S. Food and Drug Administration ("FDA") accepted the Company’s Investigational New Drug ("IND") application 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 glioblastoma ("GBM") and high-grade astrocytoma. The FDA’s safe-to-proceed within 30 days of IND filing is testimony to the talent and resourcefulness of our team, in light of the complexity of the clinical trial, which involves the interplay of 2 complex biologic agents, each with its own unique safety profile."

Financial Results:

As of September 30, 2023, Mustang’s cash and cash equivalents and restricted cash totaled $10.3 million, compared to $16.1 million at June 30, 2023, and $76.7 million as of December 31, 2022, a decrease of $5.8 million for the quarter and a decrease of $66.4 million year-to-date. Subsequent to the end of the third quarter, Mustang raised approximately $4.4 million of gross proceeds in a registered direct offering completed in October 2023.
Research and development expenses were $9.5 million for the third quarter of 2023, compared to $15.5 million for the third quarter of 2022. Non-cash, stock-based expenses included in research and development were $(19) thousand for the third quarter of 2023, compared to $0.3 million for the third quarter of 2022.
Gain on the sale of property and equipment was $1.4 million, in connection with the sale of assets to uBriGene.
General and administrative expenses were $2.1 million for the third quarter of 2023, compared to $3.4 million for the third quarter of 2022. Non-cash, stock-based expenses included in general and administrative expenses were $0.1 million for the third quarter of 2023, compared to $0.2 million for the third quarter of 2022.
Net loss attributable to common stockholders was $10.1 million, or $1.23 per share, for the third quarter of 2023, compared to a net loss attributable to common stockholders of $19.0 million, or $2.42 per share, for the third quarter of 2022.
Recent Corporate Highlights:

General Corporate:

In July 2023, Mustang announced that the Company amended its previously announced asset purchase agreement with uBriGene, the U.S. subsidiary of uBriGene Group, a leading cell and gene therapy contract development and manufacturing organization, 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 state-of-the-art clinical- and commercial-scale cell and gene therapy manufacturing facility in Worcester, Massachusetts, for upfront consideration of $6 million in cash. Mustang’s lease to the premises on which the facility is located (as well as related contracts and manufacturing personnel) did not transfer at closing because such transfer requires the consent of the landlord, which has requested an additional thirty business days to consider the proposed transfer following the landlord’s receipt of the final determination letter of the U.S. Committee on Foreign Investment in the United States ("CFIUS") regarding the transaction (as discussed further below) and a summary of Mustang’s and uBriGene’s reaction to such final determination. An additional $5 million contingent payment will be payable to Mustang upon (i) Mustang’s 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. 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 its lead product candidate, MB-106, at that site.

As previously disclosed, in connection with the sale of its manufacturing facility to uBriGene, Mustang and uBriGene previously submitted a voluntary notice with CFIUS to obtain clearance for the transaction, although obtaining such clearance was not a condition to closing the transaction. On November 13, 2023, CFIUS requested Mustang and uBriGene withdraw and re-file their joint voluntary notice to allow more time for review and discussion regarding the nature and extent of national security risk posed by the Transaction, and whether and to what extent mitigation of risk would be feasible. Upon CFIUS’s request, Mustang and uBriGene submitted a request to withdraw and re-file their joint voluntary notice. On November 13, 2023, CFIUS granted this request, accepted the joint voluntary notice and commenced a new 45-day review period commencing on November 14, 2023, which may be followed by a 45-day investigation period. Mustang and uBriGene have been and will continue to be actively engaged with CFIUS, and they remain fully committed to obtaining clearance from CFIUS and completing the full transfer of the manufacturing facility to uBriGene. There can be no assurance, however, that CFIUS will ultimately provide clearance with respect to the transaction, or what mitigating measures may be required in order to obtain such clearance.

In October 2023, Mustang completed a registered direct offering priced at-the-market for approximately $4.4 million in gross proceeds.

MB-106:

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 FL. MB-106 continues to demonstrate a favorable safety and efficacy profile in both the Fred Hutch single institution and Mustang Bio multicenter Phase 1/2 clinical trials.
In August 2023, Mustang Bio announced the first 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. Initial data show substantial clinical benefit in four of four indolent lymphoma patients, including two complete responses in FL patients, one who was previously treated with CD19 CAR-T cell therapy. From a safety perspective, 3 patients experienced Grade 1 cytokine release syndrome and no occurrences of immune effector cell-associated neurotoxicity syndrome were reported. These data align with ongoing results from the investigator-sponsored trial at Fred Hutch that show ongoing complete remission for more than three years.
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 mid-2024. Mustang Bio will report additional safety and efficacy data from the multicenter trial at the 65th ASH (Free ASH Whitepaper) Annual Meeting, taking place December 9-12, 2023, in San Diego. Finally, Mustang Bio expects to initiate a pivotal Phase 2 clinical trial in at least one additional B-cell malignancy in 2025.
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. No patients experienced CRS or immune effector cell-associated neurotoxicity syndrome over Grade 2. None of the six patients with WM have needed to start new therapy for their disease.
MB-109:

In October 2023, Mustang Bio 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.

As previously reported, preclinical data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("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. Data presented separately on MB-101 and MB-108 showed infusions were well tolerated in recurrent GBM patients. 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 31+ months, respectively. Importantly, of the 53 City of Hope ("COH") Phase 1 patients disclosed at AACR (Free AACR Whitepaper) meeting in 2022, these two complete responses were observed in the two patients with the "hottest" tumors prior to treatment with MB-101.