On September 29, 2022 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported several data presentations for mirvetuximab soravtansine (mirvetuximab) at the 2022 International Gynecologic Cancer Society (IGCS) Annual Global Meeting in New York City (Press release, ImmunoGen, SEP 29, 2022, View Source [SID1234621558]). The presentations include: consolidated efficacy and safety data from a Phase 1b/2 study evaluating mirvetuximab in combination with Avastin (bevacizumab) in folate receptor alpha (FRα)-positive recurrent ovarian cancer; the final analysis of a Phase 1b/2 study evaluating mirvetuximab in combination with carboplatin in patients with recurrent FRα-positive platinum-sensitive ovarian cancer; and the clinical benefit of mirvetuximab as a monotherapy in the SORAYA study. Two trial in progress posters from the mirvetuximab program will also be presented.

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"We are pleased with the impressive anti-tumor activity and tolerability that these mirvetuximab doublets have generated in recurrent ovarian cancer," said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. "As we await the potential FDA approval of mirvetuximab this year, we are focused on establishing mirvetuximab as both the combination agent of choice and the new standard of care as a monotherapy in folate receptor alpha positive ovarian cancer."

MIRVETUXIMAB SORAVTANSINE AND BEVACIZUMAB IN FOLATE RECEPTOR ΑLPHA-POSITIVE OVARIAN CANCER: EFFICACY IN PATIENTS WITH AND WITHOUT PRIOR BEVACIZUMAB
Lead Author: David O’Malley, MD
Date/Time: October 1, 2022, 3:55 – 5:25 PM ET
Abstract: #496

The safety and efficacy of mirvetuximab in combination with bevacizumab were evaluated in 126 patients with recurrent FRα-positive ovarian cancer. The primary endpoint for the study is confirmed objective response rate (ORR) as assessed by RECIST v1.1 and secondary endpoints include duration of response (DOR) and progression-free survival (PFS).

Key findings:

In the overall population, mirvetuximab plus bevacizumab demonstrated an ORR of 44% (95% CI, 35.6-53.6), a median DOR of 11.8 months (95% CI, 8.3-13.7), and median PFS of 8.2 months (95% CI, 6.8-9.9).
Clinical activity was observed across all levels of FRα expression, with an ORR of 52% (95% CI, 38.6–64.5), 39% (95% CI, 25.8–53.9), and 31% (95% CI, 9.1–61.4) in high, medium, and low expression, respectively.
In the bevacizumab-naïve population, anti-tumor activity was seen with an ORR of 58% (95% CI, 44.9-70.9), a median DOR of 11.8 months (95% CI, 8.3-12.9), and median PFS of 9.7 months (95% CI, 8.2-13.2).
The safety profile of mirvetuximab plus bevacizumab reflects the profile of each agent as a monotherapy; the most common treatment-related adverse events (TRAEs) were low-grade, including diarrhea (59% all grade; 2% grade 3), blurred vision (56% all grade; 1% grade 3), and fatigue (51% all grade; 4% grade 3).
"Current treatments for patients with recurrent ovarian cancer are, unfortunately, characterized by limited efficacy and challenging side effects," said David O’Malley, MD, Professor, Director of Gynecologic Oncology at the Ohio State University and the James Cancer Center. "With activity across a broad range of FRα expression regardless of prior treatment, these data support mirvetuximab plus bevacizumab as an effective combination choice for those patients who are eligible for treatment. I look forward to further evaluating this promising and novel combination in the platinum-sensitive maintenance setting in the randomized Phase 3 GLORIOSA study."

MIRVETUXIMAB SORAVTANSINE AND CARBOPLATIN FOR TREATMENT OF PATIENTS WITH RECURRENT FOLATE RECEPTOR ALPHA–POSITIVE PLATINUM-SENSITIVE OVARIAN CANCER: A FINAL ANALYSIS
Lead Author: Kathleen N. Moore, MD
Date/Time: October 1, 2022, 2:05 – 2:35 PM ET
Abstract: #499

A final analysis of the Phase 1b/2 FORWARD II study evaluating the safety, tolerability, and preliminary activity of mirvetuximab and carboplatin in patients with FRα-positive recurrent platinum-sensitive ovarian cancer was conducted.

Key findings:

In the overall efficacy evaluable patient group, the ORR was 71% (12 of 17); 18% (n=3) of patients had a CR and 53% (n=9) had a partial response.
Patients receiving mirvetuximab 6 mg/kg AIBW and carboplatin AUC5 had an ORR of 89%, median DOR of 12.1, and median PFS of 16.5 months.
Patients with medium/high FRα-expressing tumors had an ORR of 80%, median DOR of 24.2, and median PFS of 15.0 months across all escalation cohorts
The safety profile of mirvetuximab plus carboplatin reflects the safety profile of each agent as a monotherapy.
These findings support the evaluation of mirvetuximab plus carboplatin in Trial 420, a single-arm, Phase 2 study of mirvetuximab plus carboplatin in platinum-sensitive ovarian cancer patients with low, medium, or high expression of folate receptor alpha.

CLINICAL BENEFIT OF MIRVETUXIMAB SORAVTANSINE IN OVARIAN CANCER PATIENTS WITH HIGH FOLATE RECEPTOR ALPHA EXPRESSION: RESULTS FROM THE SORAYA STUDY
Lead Author: Robert L. Coleman, MD
Date/Time: September 30, 2022, 8:05 – 9:05 AM ET
Abstract: #376

SORAYA is a single-arm study of mirvetuximab in patients with platinum-resistant ovarian cancer whose tumors express high levels of FRα and who have been treated with one to three prior regimens – at least one of which included bevacizumab. Previously undisclosed waterfall plots will be presented.

Key findings:

Mirvetuximab monotherapy resulted in clinically meaningful anti-tumor activity in patients with FRα-high platinum-resistant ovarian cancer: 71% of patients experienced tumor reduction, 51% had disease control (complete response, partial response, or stable disease for ≥12 weeks), and preliminary overall survival, with 46% of events reported, was 13.8 months.
Safety and tolerability of mirvetuximab are consistent with that observed in previous studies; adverse events were primarily low-grade gastrointestinal and ocular events that generally resolved with supportive care or, if needed, dose modifications and the discontinuation rate due to TRAEs was 9%.
Mirvetuximab demonstrated a favorable benefit-risk profile in patients with FRα-high platinum-resistant ovarian cancer and has the potential to be a practice-changing, biomarker-driven therapy.
ADDITIONAL PRESENTATIONS
Trial in progress posters from ImmunoGen’s PICCOLO (Abstract #1556) trial of mirvetuximab in recurrent platinum-sensitive ovarian cancer and a Phase 2 (Abstract #1566) investigator-sponsored combination trial of mirvetuximab with Keytruda (pembrolizumab) in patients with microsatellite stable recurrent or persistent endometrial cancer will also be presented.

Additional information can be found at igcs.org.

ABOUT MIRVETUXIMAB SORAVTANSINE
Mirvetuximab soravtansine (IMGN853) is a first-in-class ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin-targeting agent, to kill the targeted cancer cells.

On September 29, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported that members of its senior management team are scheduled to participate in the BMO Biopharma Spotlight Series: Gene Editing and Therapy on Thursday, October 6, 2022, at 9:00 a.m. ET (Press release, CRISPR Therapeutics, SEP 29, 2022, View Source [SID1234621557]).

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A replay of the webcast will be archived for 14 days following the presentation on the "Events & Presentations" page in the Investors section of the Company’s website at View Source

On September 29, 2022 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science to develop a new generation of small-molecule medicines and transform how disease is treated, reported it has received a Study May Proceed Letter from the United States Food and Drug Administration (FDA) to begin a Phase 1/2 trial for CFT1946, an orally bioavailable mutant-selective BiDAC degrader for the treatment of BRAF-V600 mutant solid tumors (Press release, C4 Therapeutics, SEP 29, 2022, View Source [SID1234621555]).

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"The Study May Proceed Letter from the FDA, which marks C4T’s third successful oncology investigational new drug application in less than two years, demonstrates the power of our TORPEDO platform to build an exciting portfolio of degrader medicines that have the potential to transform how diseases are treated," said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. "We designed CFT1946 to be a potent and selective degrader of mutant BRAF-V600, which accounts for approximately 50,000 cancer diagnoses annually. We believe our innovative therapeutic candidate may overcome some limitations of BRAF inhibitor treatments to offer cancer patients the potential for deeper and more durable responses."

The Phase 1/2 clinical trial will primarily investigate safety, tolerability, and anti-tumor activity, with secondary and exploratory objectives to characterize the pharmacokinetic and pharmacodynamic profile of CFT1946. The initial arm of the Phase 1 portion of the study will evaluate CFT1946 as a single agent in patients with BRAF-V600 mutant solid tumors. As the Phase 1 trial progresses, an additional arm of the trial will evaluate CFT1946 in combination with trametinib in patients with BRAF-V600 mutant solid tumors. Following the identification of the recommended dose, the Phase 2 portion of the trial is expected to expand to three investigational arms to evaluate: (1) CFT1946 monotherapy in patients with V600 mutant melanoma or non-small cell lung cancer (NSCLC) after prior BRAF inhibitor treatment; (2) CFT1946 in combination with trametinib in patients with V600 mutant melanoma or NSCLC after prior BRAF inhibitor treatment; and (3) CFT1946 in combination with trametinib in patients with V600 mutant NSCLC who have not previously been treated with a BRAF inhibitor.

On September 29, 2022 Galecto, Inc. (NASDAQ: GLTO), a clinical stage biotechnology company focused on the development of novel treatments for fibrosis and cancer, reported positive results from a planned intermediate assessment of its ongoing Phase 2a trial of GB2064 for the treatment of myelofibrosis ("MYLOX-1 trial", NCT04679870) (Press release, Galecto Biotech, SEP 29, 2022, View Source [SID1234621554]). Fibrosis is a key disease mechanism of myelofibrosis that destroys the bone marrow function. Reducing fibrosis is required to slow the progression of the disease. Four out of five evaluable myelofibrosis patients who received GB2064 monotherapy for at least six months in the MYLOX-1 trial experienced a ≥ 1-grade reduction in collagen fibrosis of the bone marrow, an improvement suggesting that GB2064 could impact the progression of the disease and be disease modifying.

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Professor Srdan Verstovsek, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, and Principal Investigator in the MYLOX-1 trial, commented, "It is wholly unprecedented and very encouraging to observe a reduction in collagen fibrosis in this patient population. It is exciting to see the first clinical validation of LOXL2 as a fibrosis target. I very much look forward to additional developments from this ongoing study in the near future."

All four patients who experienced a > 1-grade reduction in fibrosis score also showed stable hematological parameters (hemoglobin, white blood cell count, and thrombocytes) and stable spleen volume over the six month treatment period, and none required transfusion. Two of these patients have entered the extension phase of the study due to the clinical benefit of GB2064 as evaluated by the treating physician.

Professor Claire Harrison, Guy’s & St Thomas NHS Foundation Trust, and Chair of the Safety Review Committee for the MYLOX-1 trial, commented, "It is exciting and encouraging to see a clear reduction in collagen fibrosis following the administration of a selective LOXL2 inhibitor in four of the five evaluable patients combined with stabilization of hematological parameters and spleen volume. Stable disease is excellent in a progressive disease such as myelofibrosis."

GB2064 has shown a generally acceptable tolerability profile to date. Sixteen patients have been dosed with GB2064 in the MYLOX-1 trial, of which eight patients have completed or continue to receive treatment and eight patients have either discontinued treatment as a result of an adverse event or disease progression. The most commonly observed treatment-related adverse events were gastrointestinal in nature and were manageable in most patients with standard therapy. In the five patients who completed at least six months of treatment with GB2064, there were no treatment-related serious adverse events, while in the entire trial population, the only possibly treatment-related serious adverse event was a case of fall.

Dr. Hans Schambye, President and Chief Executive Officer of Galecto, commented, "We are very excited to have demonstrated proof of principle with GB2064 showing an anti-fibrotic effect in a difficult-to-treat patient population. These intermediate results strengthen our belief that GB2064 has the potential to be a disease-modifying therapy for multiple cancers and fibrotic diseases."

Dr. Schambye continued, "With respect to our other ongoing clinical programs, we anticipate announcing top-line results from our Phase 1b/2a GULLIVER-2 trial for liver cirrhosis in the coming weeks."

Company to Host Webcast

Galecto will host a webcast event today, September 29, 2022, at 8:00 a.m. Eastern Time, to discuss the results from the intermediate assessment of the MYLOX-1 trial. Full details for the webcast are as follows:

A replay will be available on the Events portion of the Company’s investor relation’s website.

About MYLOX-1 Trial

The MYLOX-1 clinical trial is an ongoing Phase 2, open-label, single-arm study in myelofibrosis patients who are ineligible, refractory or intolerant to JAK inhibitor therapy. These patients have a progressive disease with poor quality of life, high mortality rates, and very limited treatment options. Patients receive GB2064 orally at a dose of 1000mg twice daily for nine months and undergo bone marrow biopsies at the beginning of the trial and again at months 3, 6, and 9. The primary endpoint of the ongoing MYLOX-1 trial is an assessment of safety and tolerability, while secondary endpoints focus on measurements of bone marrow fibrosis and hematological parameters. Apart from evaluating the safety and tolerability of GB2064, a key objective of the MYLOX-1 trial is to evaluate the direct anti-fibrotic activity of GB2064 by blocking lysyl oxidase-like 2 (LOXL2) in an indication that allows for repeated tissue biopsies.

As part of the planned intermediate assessment, Galecto evaluated results from the first five patients who had completed at least six months of treatment with GB2064 and who had repeated bone marrow biopsies. In the intermediate assessment, GB2064 demonstrated target engagement and penetration into the fibrotic bone marrow.

As with many ongoing clinical trials in myelofibrosis, Galecto has experienced both COVID-19-related and non-COVID-19 related challenges recruiting patients in the MYLOX-1 trial, which will delay the expected timing of data readouts. Galecto continues to evaluate whether adjustments will need to be made to the protocol for the MYLOX-1 trial to further facilitate patient recruitment. The company intends to provide an update later this year on the expected timing for full data readout of the MYLOX-1 trial.

About Myelofibrosis

Myelofibrosis is a hematological cancer that causes fibrosis of the bone marrow and disrupts the body’s normal production of blood cells, which can lead to multiple negative impacts and a significantly reduced quality of life and mortality. The bone marrow is destroyed by fibrosis, forcing out the production of blood components and aggravating symptoms, including anemia, thrombocytopenia, leukocytosis, and spleen enlargement. JAK inhibition is the current standard of care for patients with myelofibrosis; however, these therapies do not address the core of the underlying disease biology and have not shown a consistent effect on fibrosis, biomarkers of disease modification, or overall survival.

About LOXL2 and GB2064

GB2064, a potentially first-in-class, LOXL2 inhibitor candidate, is in development for the treatment of fibrotic diseases and cancer. LOXL2 is an enzyme that plays a key role in myelofibrosis and contributes to the fibrotic progression of the disease. LOXL2 catalyzes cross-linking of collagen, forming the backbone of fibrosis. The molecular target for GB2064 is LOXL2, an enzyme that plays a central role in the crosslinking of collagen in tissue fibrosis and is involved in multiple types of fibrotic diseases, including myelofibrosis. In contrast to previous attempts to inhibit LOXL2 with a monoclonal antibody, GB2064 is specifically designed to completely inhibit the LOXL2 enzymatic activity.

On September 29, 2022 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that it will hold its third-quarter 2022 sales and earnings conference call with institutional investors and analysts at 8:00 a.m. ET on Thursday, October 27 (Press release, Merck & Co, SEP 29, 2022, View Source [SID1234621552]). During the call, company executives will provide an overview of Merck’s performance for the quarter and outlook.

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Investors, journalists and the general public may access a live audio webcast of the call via this weblink. A replay of the webcast, along with the sales and earnings news release, supplemental financial disclosures, and slides highlighting the results, will be available at www.merck.com.

Participants may join the call by dialing (877) 692-8955 (USA Toll-Free) or (243) 720-6979 (USA Caller Paid). If you are calling from other countries, visit this weblink. All dial-in participants can use the access code 9646315. Journalists who wish to ask questions are requested to contact a member of Merck’s Media Relations team.