Ayala Pharmaceuticals to Host Key Opinion Leader Webinar on Desmoid Tumors

On September 29, 2022 Ayala Pharmaceuticals, Inc. (Nasdaq: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare tumors and aggressive cancers, reported that it will host a key opinion leader (KOL) webinar on unmet medical needs and evolving treatment landscape of desmoid tumors on Thursday, October 6, 2022, at 8:00 am ET (Press release, Ayala Pharmaceuticals, SEP 29, 2022, View Source [SID1234621559]).

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The webinar will include presentations by Professors Bernd Kasper, MD, Ph.D., from the Mannheim University Medical Center, and Robin Jones, MD, from The Royal Marsden Hospital and Institute of Cancer Research. Prof. Kasper will discuss the current treatment landscape for desmoid tumors and Prof. Jones will review the positive data from Part A of the ongoing Phase 2/3 RINGSIDE trial of AL102 that were presented at ESMO (Free ESMO Whitepaper) 2022.

Ayala management will provide a company update. A live Q&A session will follow the formal presentations. To register for the event, please click here.

Professor Robin Jones is Head of the Sarcoma Unit at The Royal Marsden Hospital and Team Leader in Sarcoma Clinical Trials at The Institute of Cancer Research. Professor Jones received his medical training at Guy’s and St Thomas’ Hospital and his oncology training at The Royal Marsden. Between 2010 and 2014 he was Head of the Sarcoma Program at the University of Washington/Fred Hutchinson Cancer Research Center in Seattle. His research focuses on developing novel therapies for soft tissue sarcomas and he is currently working on a number of trials of investigational agents as well as laboratory-based studies.

Professor Bernd Kasper is Chair of the Mannheim Cancer Center (MCC) at the Mannheim University Medical Center. Professor Kasper received his MD from Heidelberg University in 2000 and also studied at the Imperial College School of Medicine, Jules Bordet Institute in Brussels, and in South Kerala, India. He has a lifetime professional dedication to patient care and research in soft tissue sarcomas, desmoid-type fibromatosis, and gastrointestinal stromal tumors and is the Principal Investigator of several national and international trials.

AL102 is being evaluated in the ongoing RINGSIDE pivotal Phase 2/3 clinical trial in desmoid tumors. Positive interim results from Part A, the Phase 2 segment of this study, were presented at ESMO (Free ESMO Whitepaper) 2022, showing efficacy across all cohorts, with early tumor responses that deepened over time. AL102 was well tolerated, which could allow for long term treatment of patients. The company has initiated Part B of RINGSIDE (Phase 3), as well as enrolling patients in an open label extension study.

About the RINGSIDE study
The RINGSIDE pivotal Phase 2/3 study is a randomized global multi-center trial. Part A of the study is evaluating the efficacy, safety, tolerability, and tumor volume by MRI after 16 weeks of AL102 in patients with desmoid tumors. It enrolled 42 patients and is evaluating 3 doses of AL102. Patients who participated in Part A are eligible to enroll into an open-label extension study at the Part B selected dose of 1.2 mg daily, and long-term efficacy and safety will be monitored.

Part B of the study, the Phase 3 segment, has been initiated. This is a double-blind, placebo-controlled segment enrolling up to 156 patients with progressive disease, comparing AL102 at 1.2 mg once daily to placebo. The primary endpoint for Part B is progression-free survival (PFS) with secondary endpoints including objective response rate (ORR), duration of response (DOR), tumor volume reduction, and patient-reported Quality of Life (QOL) measures. For more information on the RINGSIDE Phase 2/3 study with AL102 for the treatment of desmoid tumors, please visit ClinicalTrials.gov and reference Identifier NCT04871282 (RINGSIDE).

About Desmoid Tumors
Desmoid tumors, also called aggressive fibromatosis or desmoid-type fibromatosis, are rare connective tissue tumors that typically arise in the upper and lower extremities, abdominal wall, head and neck area, mesenteric root, and chest wall with the potential to arise in additional parts of the body. Desmoid tumors do not metastasize, but often aggressively infiltrate neurovascular structures and vital organs. People living with desmoid tumors are often limited in their daily life due to chronic pain, functional deficits, general decrease in their quality of life and organ dysfunction. Desmoid tumors have an annual incidence of approximately 1,700 patients in the United States and typically occur in patients between the ages of 15 and 60 years. They are most commonly diagnosed in young adults between 30-40 years of age and are more prevalent in females. Today, surgery is no longer regarded as the cornerstone treatment of desmoid tumors due to a high rate of recurrence post-surgery and there are currently no FDA-approved systemic therapies for the treatment of unresectable, recurrent or progressive desmoid tumors.

ImmunoGen Presents Comprehensive Updates for Mirvetuximab Soravtansine Combination Data in Ovarian Cancer at IGCS

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.

CRISPR Therapeutics to Present at the BMO Biopharma Spotlight Series: Gene Editing and Therapy

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

C4 Therapeutics Receives Study May Proceed Letter from U.S. FDA to Initiate Phase 1/2 Clinical Trial of CFT1946, an Orally Bioavailable BiDAC™ Degrader, in BRAF-V600 Mutant Solid Cancers

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.

GB2064 Shows Reduction in Fibrosis of the Bone Marrow in Patients with Myelofibrosis, Validating LOXL2 as a Clinical Fibrosis Target

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.