On March 7, 2024 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported an update on its recent corporate progress and announced financial results for the year ended December 31, 2023 (Press release, MacroGenics, MAR 7, 2024, View Source [SID1234640928]).

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"We expect that 2024 will be an important year for MacroGenics, with multiple pipeline advancements anticipated," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "Late last year, we completed enrollment of 177 patients in the TAMARACK Phase 2 study of vobra duo, which was ahead of schedule. We plan to present the initial TAMARACK clinical data in the second quarter of this year. Later in the year, we expect to share updated clinical data from the trial. In addition, we continue to enroll the LORIKEET Phase 2 study of lorigerlimab in mCRPC and expect to start enrolling patients in the dose expansion portion of the combination study of vobra duo and lorigerlimab. Finally, we are excited about the potential of our topoisomerase I inhibitor-based ADCs, including MGC026, for which we recently began a Phase 1 study, and MGC028, for which we anticipate submitting an IND by year end."

Updates on Proprietary Investigational Programs

Recent progress and anticipated events related to MacroGenics’ investigational product candidates are highlighted below.

Vobramitamab duocarmazine (vobra duo) is an antibody-drug conjugate (ADC) that targets B7-H3, an antigen with broad expression across multiple solid tumors and a member of the B7 family of molecules involved in immune regulation.
MacroGenics completed enrollment of the TAMARACK Phase 2 study of vobra duo in November 2023. A total of 177 patients have been dosed in the study, exceeding the study design goal of 100 participants. TAMARACK is being conducted in patients with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with one prior androgen receptor axis-targeted therapy (ARAT). Participants may have received up to one prior taxane-containing regimen, but no other chemotherapy agents. The TAMARACK study is designed to evaluate vobra duo at two different doses: 2.0 mg/kg or 2.7 mg/kg every four weeks (q4W).

In late January 2024, the TAMARACK independent data safety monitoring committee (IDSMC) recommended continuing the study. Also, in early February, MacroGenics submitted an abstract to the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper) that included the safety data reviewed by the IDSMC, based on a January 2024 data cut-off. The Company anticipates presenting updated safety and preliminary efficacy data at ASCO (Free ASCO Whitepaper).
MacroGenics intends to expand the TAMARACK study of vobra duo by enrolling patients with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), melanoma, squamous cell carcinoma of the head and neck (SCCHN) and anal cancer. The Company expects to initiate dosing in these additional cohorts in mid-2024.
MacroGenics continues to enroll a Phase 1/2 dose escalation study of vobra duo in combination with lorigerlimab in patients with various advanced solid tumors. The Company anticipates commencing a dose expansion study of this combination in mCRPC and at least one additional indication in 2024.
Lorigerlimab is a bispecific, tetravalent PD-1 × CTLA-4 DART molecule. MacroGenics is enrolling LORIKEET, a randomized Phase 2 study of lorigerlimab in combination with docetaxel vs. docetaxel alone in second-line, chemotherapy-naïve mCRPC patients. A total of 150 patients are planned to be treated in the 2:1 randomized study. The current trial design includes a primary study endpoint of radiographic progression-free survival (rPFS). The Company anticipates providing a study update in the second half of 2024.
MGD024 is a next-generation, humanized CD123 × CD3 DART molecule designed to minimize cytokine-release syndrome, while maintaining anti-tumor cytolytic activity, and permitting intermittent dosing through a longer half-life. MacroGenics continues to enroll patients in a Phase 1 dose-escalation study of MGD024 in patients with CD123-positive neoplasms, including acute myeloid leukemia and myelodysplastic syndromes.
MGC026 is a clinical ADC directed against B7-H3, incorporating a novel site-specific linker and topoisomerase I inhibitor-based cytotoxic payload developed by Synaffix (a Lonza company). With distinct mechanisms of action, vobra duo and MGC026 may address different cancers, tumor stages, or be used in combination with alternate agents — or potentially with one another — to enhance their clinical utility. The Company plans to present MGC026 preclinical data at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2024. MacroGenics recently initiated a Phase 1 dose escalation study of MGC026 in patients with advanced solid tumors.
MGC028 is a preclinical ADC incorporating an ADAM9-targeting antibody and represents the second MacroGenics ADC molecule that incorporates Synaffix’s novel site-specific linker and topoisomerase I inhibitor-based cytotoxic payload. ADAM9 (a disintegrin and metalloprotease domain 9) is a member of the ADAM family of multifunctional type 1 transmembrane proteins that play a role in tumorigenesis and cancer progression and is overexpressed in multiple cancers, making it an attractive target for cancer treatment. MacroGenics plans to present preclinical data for MGC028 at the upcoming AACR (Free AACR Whitepaper) Annual Meeting in April and currently anticipates submitting an investigational new drug (IND) application for MGC028 by the end of 2024.

MGC028 is the second ADAM9-targeted ADC that MacroGenics has pursued. The first was IMGC936, a molecule with a maytansinoid payload that was advanced under a co-development arrangement with ImmunoGen, Inc. (ImmunoGen, now part of AbbVie). Under the 50/50 collaboration, ImmunoGen led clinical development and completed initial Phase 1 dose escalation and dose expansion studies. Neither MacroGenics nor AbbVie intends to further pursue development of IMGC936 as the molecule did not achieve pre-established clinical safety and efficacy benchmarks. The Company believes ADAM9 remains a promising target for delivery of an alternative cytotoxic payload.
Enoblituzumab is an Fc-optimized monoclonal antibody that targets B7-H3. MacroGenics’ academic collaborators have initiated the HEAT study, an investigator-sponsored, randomized Phase 2 clinical trial. This study will evaluate the activity of neoadjuvant enoblituzumab given prior to radical prostatectomy in up to 219 men with high-risk localized prostate cancer.
2023 Financial Results

Cash Position: Cash, cash equivalents and marketable securities balance as of December 31, 2023, was $229.8 million, compared to $154.3 million as of December 31, 2022.
Revenue: Total revenue was $58.7 million for the year ended December 31, 2023, compared to total revenue of $151.9 million for the year ended December 31, 2022. The decrease was primarily due to a decrease in revenue from collaborative and other agreements.
R&D Expenses: Research and development expenses were $166.6 million for the year ended December 31, 2023, compared to $207.0 million for the year ended December 31, 2022. The decrease was primarily due to decreased manufacturing-related costs for vobra duo, decreased development and clinical trial costs related to margetuximab, and decreased costs related to discontinued studies, partially offset by increased expenses related to MGC026 and MGC028 development.
SG&A Expenses: Selling, general and administrative expenses were $52.2 million for the year ended December 31, 2023, compared to $58.9 million for the year ended December 31, 2022. The decrease was primarily related to decreased selling costs for MARGENZA.
Other Income: During the year ended December 31, 2023, MacroGenics received $100.0 million proceeds from the sale of its single-digit royalty interest on global net sales of TZIELD to DRI Healthcare Acquisitions LP. In addition, the Company received a $50.0 million milestone payment from Sanofi S.A. related to the achievement of a primary endpoint in a TZIELD clinical study. Under GAAP guidelines and pursuant to Financial Accounting Standards Board’s Accounting Standards Codification 470, this combined $150.0 million was included in Other Income as a "Gain on royalty monetization arrangement" in 2023.
Net Loss: Net loss was $9.1 million for the year ended December 31, 2023, compared to net loss of $119.8 million for the year ended December 31, 2022.
Shares Outstanding: Shares of common stock outstanding as of December 31, 2023 were 62,070,627.
Cash Runway Guidance: MacroGenics anticipates that its cash, cash equivalents and marketable securities balance of $229.8 million as of December 31, 2023, in addition to projected and anticipated future payments from partners and product revenues should extend its cash runway into 2026. The Company’s expected funding requirements reflect anticipated expenditures related to the Phase 2 TAMARACK clinical trial, the Phase 2 LORIKEET study as well as MacroGenics’ other ongoing clinical and preclinical studies.
Conference Call Information

To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call.

The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source A recorded replay of the webcast will be available shortly after the conclusion of the call and archived on MacroGenics’ website for 30 days following the call.

On March 7, 2024 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, reported its fourth quarter and full year 2023 financial and operating results and will host a conference call today at 4:30 p.m. Eastern Time to discuss these results and provide a business update (Press release, Lineage Cell Therapeutics, MAR 7, 2024, View Source [SID1234640927]).

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"Throughout 2023, our team has continued to advance our clinical and preclinical pipeline of differentiated cell transplant programs," stated Brian M. Culley, Lineage CEO. "The most important area of attention has remained our partnership with Roche and Genentech and the support we provide to the ongoing Phase 2a clinical study of OpRegen in patients with geographic atrophy secondary to AMD. With the recent clearance of our IND amendment for OPC1, we are excited for the opportunity to return this program back into the clinic in both subacute and, for the first time, chronic spinal cord injury patients. Following the closing of our recent financing, a transaction conducted without a discount or warrants, our balance sheet has been strengthened, which will help us advance our programs and reach important milestones this year that can help provide a meaningful impact for patients."

2023 Select Development Highlights

RG6501 (OpRegen)
Continued execution under our collaboration with Roche and Genentech across multiple functional areas, including support for the ongoing Phase 2a clinical study in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Long-term follow-up of patients from the Phase 1/2a clinical study of OpRegen:
Positive clinical data presented at 2023 Eyecelerator, 23rd EU RETINA Congress, and 2023 ARVO Annual Meetings.
U.S. Patent No.11,746,324 entitled "Large Scale Production of Retinal Pigment Epithelial Cells," issued.
OPC1
Submitted an Investigational New Drug Amendment (INDa) for OPC1 for the treatment of chronic and subacute spinal cord injury to enable initiation of DOSED (Delivery of Oligodendrocyte Progenitor Cells for Spinal Cord Injury: Evaluation of a Novel Device) clinical study in subacute and chronic spinal cord patients. INDa clearance from the U.S. Food and Drug Administration announced in February 2024.
Received CIRM grant to support the 1st Annual Spinal Cord Injury Investor Symposium, hosted in partnership with the Christopher & Dana Reeve Foundation.
Preclinical Programs
Reported positive ANP1 initial proof of concept results from collaboration with the University of Michigan; initial results demonstrated delivery, engraftment, and survival of ANP1 cells into specific target areas, supporting advancement of program into functional preclinical testing.
Initiated development activities for hypoimmune pluripotent cell line for neurology indications under collaboration with Eterna Therapeutics.
Balance Sheet Highlights

Cash, cash equivalents, and marketable securities of $35.5 million as of December 31, 2023, together with the approximate $13.8 million in net proceeds from the registered direct offering of our common shares completed in February 2024, is expected to support planned operations into Q3 2025.

Fourth Quarter Operating Results

Revenues: Lineage’s revenue is generated primarily from collaboration revenues and royalties. Total revenues for the three months ended December 31, 2023 were approximately $2.1 million, a net increase of $0.2 million as compared to $1.9 million for the same period in 2022.

Operating Expenses: Operating expenses are comprised of research and development ("R&D") expenses and general and administrative ("G&A") expenses. Total operating expenses for the three months ended December 31, 2023 were $8.2 million, a decrease of $0.3 million as compared to $8.5 million for the same period in 2022.

R&D Expenses: R&D expenses for the three months ended December 31, 2023 were $3.9 million, a decrease of $0.2 million as compared to $4.1 million for the same period in 2022. The net decrease was primarily driven by $0.2 million in OpRegen program expenses and $0.4 million for other research and development expense programs, partially offset by $0.2 million in OPC1 program expenses and $0.2 million for preclinical programs.

G&A Expenses: G&A expenses for the three months ended December 31, 2023 of $4.3 million were in line with expenses for the same period in 2022.

Loss from Operations: Loss from operations for the three months ended December 31, 2023 was $6.4 million, a decrease of $0.2 million as compared to $6.6 million for the same period in 2022.

Other Income/(Expenses), Net: Other income/(expenses), net for the three months ended December 31, 2023 reflected other income of $1.6 million, compared to other income of $0.3 million for the same period in 2022. The net change was primarily driven by exchange rate fluctuations related to Lineage’s international subsidiaries and fair market value changes in marketable equity securities.

Net Loss Attributable to Lineage: The net loss attributable to Lineage for the three months ended December 31, 2023 was $4.8 million, or $0.03 per share (basic and diluted), compared to a net loss of $6.4 million, or $0.03 per share (basic and diluted), for the same period in 2022.

Full Year Operating Results

Revenues: Lineage’s revenue is generated primarily from licensing fees, collaboration revenues, royalties, and research grants. Total revenues for the year ended December 31, 2023 were $8.9 million, a decrease of $5.8 million as compared to $14.7 million for the same period in 2022. The decrease was primarily driven by lower collaboration and licensing revenue recognized from deferred revenues under the collaboration and license agreement with Roche.

Operating Expenses: Operating expenses are comprised of R&D expenses and G&A expenses. Total operating expenses for the year ended December 31, 2023 were $33.0 million, a decrease of $3.5 million as compared to $36.5 million for the same period in 2022.

R&D Expenses: R&D expenses for the year ended December 31, 2023 were $15.7 million, an increase of $1.7 million as compared to $14.0 million for the same period in 2022. The increase was primarily driven by $0.4 million in OpRegen program expenses, $1.2 million in OPC1 program expenses, and $2.0 million in preclinical programs. These increases were partially offset by $1.9 million in other research and development programs, primarily related to reduced manufacturing activities.

G&A Expenses: G&A expenses for the year ended December 31, 2023 were $17.3 million, a decrease of approximately $5.2 million as compared to $22.5 million for the same period in 2022. The decrease was primarily attributable to $4.2 million in lower litigation and legal expenses, as well as an overall reduction in costs incurred for services provided by third parties, consulting costs, and rent-related expenses.

Loss from Operations: Loss from operations for the year ended December 31, 2023 was $24.7 million, an increase of $2.2 million as compared to $22.5 million for the same period in 2022.

Other Income/(Expenses), Net: Other income (expenses), net for the year ended December 31, 2023 reflected other income of $1.5 million, compared to other expense of ($3.3) million for the same period in 2022. The net change was primarily attributable to fluctuations in intercompany balances and related exchange rates applicable to Lineage’s international subsidiaries, as well as fair market value changes in marketable equity securities.

Net Loss Attributable to Lineage: The net loss attributable to Lineage for the year ended December 31, 2023 was $21.5 million, or $0.12 per share (basic and diluted), compared to a net loss of $26.3 million, or $0.15 per share (basic and diluted), for 2022.

Conference Call and Webcast

Interested parties may access the conference call on March 7th, 2024, by dialing (800) 715-9871 from the U.S. and Canada and should request the "Lineage Cell Therapeutics Call." A live webcast of the conference call will be available online in the Investors section of Lineage’s website. A replay of the webcast will be available on Lineage’s website for 30 days and a telephone replay will be available through March 14, 2024, by dialing (800) 770-2030 from the U.S. and Canada and entering conference ID number 8345585.

On March 7, 2024 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company creating and developing engineered IgM antibodies, reported its financial results for the fourth quarter and full year ended December 31, 2023 and provided an update on recent developments (Press release, IGM Biosciences, MAR 7, 2024, View Source [SID1234640926]).

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"We made significant progress during 2023 in the clinical development of our two lead product candidates in therapeutic areas that we believe have the greatest potential to produce significant near-term value," said Fred Schwarzer, Chief Executive Officer of IGM Biosciences. "Enrollment in our randomized clinical trial of aplitabart plus FOLFIRI and bevacizumab in second-line metastatic colorectal cancer continues to be encouraging, and we expect to expeditiously complete our target enrollment of 110 patients. If the control arm of this randomized study demonstrates the expected median progression free survival of approximately six months, we will be able to begin evaluating the benefit of aplitabart in enhancing progression free survival by the end of this year."

Mr. Schwarzer continued, "We also initiated two Phase 1b clinical trials of imvotamab in severe systemic lupus erythematosus and in severe rheumatoid arthritis. We are encouraged by the initial level of investigator and patient interest that we have seen in these clinical trials, and we are optimistic that we will be able to generate meaningful initial clinical data by the end of 2024."

Pipeline Updates

Aplitabart (DR5 agonist)

Clinical development of aplitabart advances.
Enrollment ongoing in randomized colorectal cancer clinical trial. The Company continues to enroll patients in a randomized clinical trial of aplitabart, a death receptor 5 agonist, plus FOLFIRI and bevacizumab in second-line metastatic colorectal cancer. In addition to clinical trial sites in the United States, this study includes multiple clinical trial sites in Asia and Europe. This randomized trial is designed to assess the additional benefit of 3 mg/kg of aplitabart when administered in combination with the current standard of care treatment arm of FOLFIRI and bevacizumab, with a primary endpoint of progression-free survival (PFS).
Evaluating 10 mg/kg dose in single arm colorectal cancer clinical trial. The Company also continues to evaluate a dose of 10 mg/kg of aplitabart in combination with FOLFIRI and bevacizumab in the treatment of later line colorectal cancer patients in its single arm combination clinical trial. The Company expects to complete enrollment of patients in this 10 mg/kg single arm combination dose cohort in the first half of 2024.
Imvotamab (CD20 x CD3)

Clinical development of imvotamab in autoimmune diseases advances. The Company currently has two Phase 1b clinical trials underway for imvotamab, an IgM-based CD20 x CD3 bispecific T cell engaging antibody: one in severe systemic lupus erythematosus (SLE) and one in severe rheumatoid arthritis (RA). These clinical trials are being expanded to include multiple U.S. and international clinical trial sites. The Company also received clearance in late 2023 from the FDA of its IND application for the use of imvotamab in treating idiopathic inflammatory myopathies (myositis), and the Company is currently making preparations to initiate this clinical trial.
IGM-2644 (CD38 x CD3)

Clinical development of IGM-2644 in autoimmune diseases to be initiated. The Company is currently making plans to begin clinical development of IGM-2644, a CD38 x CD3 T cell engager antibody, in the treatment of autoimmune diseases.
Fourth Quarter and Full Year 2023 Financial Results

Cash and Investments: Cash and investments as of December 31, 2023 were $337.7 million, compared to $427.2 million as of December 31, 2022.
Collaboration Revenue: For the fourth quarter and year ended 2023, collaboration revenues were $0.7 million and $2.1 million, respectively, compared to $0.4 million and $1.1 million for the fourth quarter and year ended 2022, respectively.
Research and Development (R&D) Expenses: For the fourth quarter and year ended 2023, R&D expenses were $54.2 million and $215.5 million, respectively, compared to $45.0 million and $179.3 million for the fourth quarter and year ended 2022, respectively.
General and Administrative (G&A) Expenses: For the fourth quarter and year ended 2023, G&A expenses were $11.6 million and $50.1 million, respectively, compared to $11.6 million and $49.7 million for the fourth quarter and year ended 2022, respectively.
Net Loss: For the fourth quarter of 2023, net loss was $60.7 million, or a loss of $1.01 per share, compared to a net loss of $52.6 million, or a loss of $1.19 per share, for the fourth quarter of 2022. For the year ended 2023, net loss was $246.4 million, or a loss of $4.71 per share, compared to a net loss of $221.1 million, or a loss of $5.32 per share, for the year ended 2022.
2024 Financial Guidance

The Company expects full year 2024 GAAP operating expenses of $210 million to $220 million, including estimated non-cash stock-based compensation expense of approximately $40 million, and full year collaboration revenue of approximately $3 million related to the Sanofi agreement. The Company expects to end 2024 with a balance of approximately $180 million in cash and investments, and for the balance to enable it to fund its operating expenses and capital expenditure requirements into the second quarter of 2026.

On March 7, 2024 GSK plc (LSE/NYSE: GSK) reported positive headline results from an interim analysis of the DREAMM-8 phase III head-to-head trial evaluating Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex), versus a standard of care, bortezomib plus PomDex, as a second line and later treatment for relapsed or refractory multiple myeloma (Press release, GlaxoSmithKline, MAR 7, 2024, View Source [SID1234640925]). The trial met its primary endpoint of progression-free survival (PFS) at a pre-specified interim analysis and was unblinded early based on the recommendation by an Independent Data Monitoring Committee (IDMC).

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The belantamab mafodotin combination significantly extended the time to disease progression or death versus the standard of care combination. A positive overall survival (OS) trend favouring the Blenrep combination was also observed at the time of this analysis. The trial continues to follow up for OS. The safety and tolerability of the belantamab mafodotin regimen were broadly consistent with the known safety profile of the individual agents.

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "The results seen in both DREAMM-7 and DREAMM-8 provide strong clinical evidence of the robust efficacy shown with belantamab mafodotin in use with standard of care combinations. We now look forward to discussing these data with regulators. If approved, we believe these combinations have the potential to redefine the treatment of relapsed or refractory multiple myeloma and advance the standard of care. This is exciting news for patients given the high unmet medical need for both efficacious and easily administered therapies with differing mechanisms of action."

DREAMM-8 is the second phase III head-to-head belantamab mafodotin combination trial in second line and later treatment for multiple myeloma to report positive results. Positive findings from DREAMM-7, a phase III head-to-head trial evaluating belantamab mafodotin in combination with bortezomib and dexamethasone (BorDex) versus daratumumab plus BorDex in the same treatment setting, were presented1 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series on 6 February 2024. Detailed findings from DREAMM-8 will be presented at a future medical congress and shared with regulatory authorities.

About DREAMM-8
The DREAMM-8 phase III clinical trial is a multicentre, open-label, randomised trial evaluating the efficacy and safety of belantamab mafodotin in combination with PomDex compared to a combination of bortezomib and PomDex in patients with relapsed/refractory multiple myeloma previously treated with at least one prior line of multiple myeloma therapy, including a lenalidomide-containing regimen, and who have documented disease progression during or after their most recent therapy.

A total of 302 participants were randomised at a 1:1 ratio to receive either belantamab mafodotin plus PomDex, or bortezomib plus PomDex.

The primary endpoint is PFS. Secondary endpoints include OS, overall response rate, duration of response, minimal residual disease negativity as assessed by next-generation sequencing, safety, and patient-reported and quality of life outcomes.

About multiple myeloma
Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.2,3 There are approximately 176,000 new cases of multiple myeloma diagnosed globally each year.4 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.5

About Blenrep
Blenrep is an antibody-drug conjugate comprising a humanised B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.

Refer to the Blenrep UK Summary of Product Characteristics6 for a full list of adverse events and the complete important safety information in the United Kingdom.

On March 7, 2024 Foghorn Therapeutics Inc. (Nasdaq: FHTX), a clinical-stage biotechnology company pioneering a new class of medicines that treat serious diseases by correcting abnormal gene expression, reported a financial update and corporate outlook in conjunction with the Company’s 10-K filing for the year ending December 31, 2023 (Press release, Foghorn Therapeutics, MAR 7, 2024, View Source [SID1234640924]). With an initial focus in oncology, Foghorn’s Gene Traffic Control Platform and resulting broad pipeline have the potential to transform the lives of people with a wide spectrum of diseases.

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"The research and clinical advances we made in 2023 set the stage for Foghorn to deliver significant value with the potential for several differentiated, high-impact medicines in 2024 and beyond," said Adrian Gottschalk, President and Chief Executive Officer of Foghorn. "In 2023 we initiated a combination study with FHD-286 in AML, with data anticipated in the second half of 2024. Based on the mutation-agnostic differentiation effect observed in our single-agent escalation study, we believe FHD-286 has the potential to be a first-in-class broad-based differentiation therapeutic in AML. We are also making progress with our selective BRM program with FHD-909, a first-in-class BRM selective inhibitor, selected for clinical development by partner Lilly. The IND is planned for the second quarter of 2024, with an initial focus in non-small cell lung cancer. Finally, we are excited by the preclinical efficacy and safety data for our CBP and EP300 selective degrader programs and target IND-enabling studies for CBP by the end of the year. Our cash position remains strong with runway into the first half of 2026."

Key Recent Updates and Upcoming Milestones

•FHD-286. FHD-286 is a potent, selective inhibitor of the BRG1 and BRM subunits of the BAF chromatin remodeling complex where dependency on BRG1/BRM is well-established preclinically with multiple tumor types, including acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS), non-small cell lung cancer (NSCLC) and prostate cancer.
•AML Update. Foghorn commenced a Phase 1 study of FHD-286 in combination with decitabine or low-dose cytarabine (LDAC) in relapsed and/or refractory AML patients, with the first patient dosed during the third quarter of 2023. Dose escalation is ongoing, and the first clinical data are expected in the second half of 2024.
•TKI Resistance. Recently published data, along with Foghorn’s work, suggest that FHD-286 may play an important role in overcoming resistance in EGFR/KRAS tumors. The Company is conducting preclinical work to further explore the opportunity and expects data in the second quarter of 2024.

•Differentiated Pipeline Advancement. Foghorn continues to expand its platform and pipeline. The Company anticipates the potential for six new investigational new drug (IND) applications in the next four years. The Company continues to progress programs for multiple targets that include chromatin remodeling complexes, transcription factors, helicases, and other chromatin-related factors. These targets include selective BRM and wholly owned programs including CBP, EP300, and ARID1B, as well as other undisclosed targets, which combined could address more than 20 tumor types impacting more than 500,000 new patients annually.
•Selective CBP and Selective EP300 programs. Foghorn is presenting new preclinical data for its CBP and EP300 selective degrader programs at the 2024 AACR (Free AACR Whitepaper) Annual Meeting, April 5-10, 2024.
•CBP selective degraders have shown significant tumor growth inhibition in a colorectal cancer in vivo model. Antiproliferative effects were also observed for numerous cancer cell lines, including colorectal, gastric and bladder cancers.
•EP300 selective degraders have shown potent cellular antiproliferation and in vivo tumor growth inhibition in an AR+ enzalutamide prostate in vivo model.
•At preclinical efficacious doses, neither the CBP nor the EP300 selective degraders cause thrombocytopenia, a commonly observed safety liability for dual CBP/EP300 inhibitors.

•Lilly Collaboration. Foghorn is engaged in a strategic collaboration with Lilly and continues to advance the BRM selective inhibitor and degrader programs along with other undisclosed programs.
◦In the first quarter of 2024, Lilly selected FHD-909, a first-in-class oral BRM selective inhibitor, for clinical development. Lilly plans to file an IND for FHD-909 in the second quarter of 2024. The primary target patient population is BRG1-mutated NSCLC.

◦Selective BRM inhibition has been a sought-after objective in cancer research for many years. A variety of tumor types, including NSCLC, are known to have mutations in BRG1, which we believe make them dependent on BRM activity for their survival. Selective blocking of BRM activity is considered a promising strategy for causing tumor cell death while sparing healthy cells.
◦Preclinical data will be presented in 2024, including at AACR (Free AACR Whitepaper) with a poster presentation on April 8.

In December 2021, Foghorn announced a strategic collaboration with Lilly to create novel oncology medicines. The collaboration includes a co-development and co-commercialization agreement for Foghorn’s Selective BRM oncology program and an additional undisclosed oncology target. In addition, the collaboration includes three discovery programs using Foghorn’s proprietary Gene Traffic Control platform.

Full Year 2023 Financial Highlights

•Collaboration Revenues. Collaboration revenues were $34.2 million for the year ended December 31, 2023, compared to $19.2 million for the year ended December 31, 2022. The increase year-over-year was primarily driven by revenue recognized under the Merck collaboration due to the termination of the agreement and the subsequent recognition of the remaining deferred revenue.

•Research and Development Expenses. Research and development expenses were $109.7 million for the year ended December 31, 2023, compared to $105.6 million for the year ended December 31, 2022. This increase was primarily due to costs associated with continued investment in R&D personnel, platform, and other early-stage research, partially offset by a decrease in spend on FHD-286 and FHD-609.

•General and Administrative Expenses. General and administrative expenses were $32.4 million for the year ended December 31, 2023, compared to $30.7 million for the year ended December 31, 2022. This increase was primarily due to an increase in investments to support the growing business, which included increases in personnel-related costs and stock-based compensation expense.

•Net Loss. Net loss was $98.4 million for the year ended December 31, 2023, compared to a net loss of $108.9 million for the year ended December 31, 2022.

•Cash, cash equivalents and marketable securities. As of December 31, 2023, the Company had $234.1 million in cash, cash equivalents and marketable securities, providing cash runway into the first half of 2026.

About FHD-286
FHD-286 is a highly potent, selective, allosteric, and orally available small-molecule, enzymatic inhibitor of BRG1 (SMARCA4) and BRM (SMARCA2), two highly similar proteins that are the ATPases, or the catalytic engines, of the BAF complex, one of the key regulators within the chromatin regulatory system. In preclinical studies, FHD-286 has shown anti-tumor activity across a broad range of malignancies including both hematologic and solid tumors.

About AML
Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and the most common type of acute leukemia in adults. AML is a diverse disease associated with multiple genetic mutations. It is diagnosed in about 20,000 people every year in the United States.

About FHD-909
FHD-909 (a.k.a. LY4050784) is a highly potent, allosteric and orally available small molecule that selectively inhibits the ATPase activity of BRM (SMARCA2) over its closely related paralog BRG1 (SMARCA4), two proteins that are the catalytic engines across all forms of the BAF complex, one of the key regulators of the chromatin regulatory system. In preclinical studies, tumors with mutations in BRG1 rely on BRM for BAF function. FHD-909 has shown significant anti-tumor activity across multiple BRG1-mutant lung tumors.