On September 29, 2022 Propanc Biopharma, Inc. (OTC Pink: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that Chief Scientific Officer and Co-Founder, Dr Julian Kenyon, MD, MB, ChB, explains why pancreatic and ovarian cancers are selected as the primary target therapeutic indications for planned PRP human studies (Press release, Propanc, SEP 29, 2022, View Source [SID1234621563]). According to Dr Kenyon, target indications were selected based on in vitro and in vivo data, as well as clinical observations from a compassionate use study investigating the effects of two proenzymes, trypsinogen and chymotrypsinogen against a range of malignant tumors. Overall, proenzymes appeared to exert significant effects against more aggressive, less differentiated tumor types, like pancreatic and ovarian tumors. Patients from the compassionate use study suffering from cancers of the GI tract, or endocrine tumors, such as pancreatic and ovarian cancers, benefited most from treatment. The world market for pancreatic and ovarian cancer drugs is projected to grow to $4.2 Billion in 2025 according to Grandview Research and $10.1 Billion by 2027 according to iHealthcareAnalyst, respectively, resulting in a combined global market of $14.3 Billion over the next 5-year period.

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Extensive laboratory analysis confirmed that PRP reduced the main characteristics of cancer spread, namely angiogenesis (blood vessel formation), which is a critical step in tumor development, as well as the spreading of tumor metastases. In addition, assays revealed that the migration capacity of ovarian, pancreatic, melanoma and colon cancer cells was suppressed after incubation with PRP. Furthermore, evidence suggests the epithelial to mesenchymal transition (EMT), a biological process associated with wound healing and cell migration, which causes cancer stem cells (CSCs) to become motile and invasive, is associated with metastasis and inducing drug resistance in many cancers, such as pancreatic and ovarian cancers. Studies in pancreatic and cancer cell lines after PRP treatment demonstrated a significant reduction in EMT markers and genes and in fact, a reversal of the EMT process so that CSCs become benign and less resistant to standard treatments.

The in vivo effects of PRP at different doses on tumor weight in implanted pancreatic and ovary tumors was evaluated. In the pancreatic tumor model, there was significant reduction in mean tumor weight in animals treated for 26 days with PRP with more than 85% tumor growth inhibition compared with the control. Furthermore, ovary tumor-bearing mice showed a significant reduction in mean tumor weight in animals treated for 21 days with two different doses of PRP, resulting in a 46 – 52% tumor growth inhibition compared with the control.

The clinical efficacy of a suppository formulation containing bovine pancreatic proenzymes trypsinogen and chymotrypsinogen was evaluated in the context of a UK Pharmaceuticals Special Scheme and the results were published in Scientific Reports. Clinical effects were studied in 46 patients with advanced metastatic cancers of different origin (prostate, breast, ovarian, pancreatic, colorectal, stomach, non-small cell lung, bowel cancer and melanoma) after treatment with a rectal formulation of both pancreatic proenzymes. No severe or serious adverse events related to the rectal administration were observed. Patients did not experience any hematological side effects as typically seen with classical chemotherapy regimens.

In order to assess the therapeutic activity, overall survival of patients under treatment was compared to the life expectancy assigned to a patient prior to treatment start. Nineteen from 46 patients (41.3%) with advanced malignant diseases, most of them suffering from metastases, had a survival time significantly longer than their expected, in fact, for the whole set of cancer types, mean survival (9.0 months) was significantly higher than mean life expectancy (5.6 months). In the case of pancreatic and ovarian cancers, 2 from 4 pancreatic cancer patients and 4 from 7 ovarian cancer patients significantly exceeded life expectancy.

As a result of the extensive studies undertaken, particularly in pancreatic cancer, the Company applied for and received Orphan Drug Designation (ODD) from the US Food and Drug Administration (USFDA) for the use of its lead product, PRP, for the treatment of pancreatic cancer. The approved indication is one of the most lethal malignancies with a median survival of 6 months and a 5-year survival rate of less than 5%. The lethal nature of this disease stems from its propensity to rapidly disseminate to the lymphatic system and distant organs, and is a major unmet medical issue. Under the Orphan Drug Act (ODA), drugs, vaccines, and diagnostic agents qualify for orphan status if they are intended to treat a disease affecting less than 200,000 American citizens. Under the ODA, orphan drug sponsors qualify for seven-year FDA-administered market Orphan Drug Exclusivity (ODE), tax credits of up to 50% of R&D costs, R&D grants, waived FDA fees, protocol assistance and may get clinical trial tax incentives.

"Over the past 15 years, our extensive research has uncovered a truly unique and exciting technology that selectively targets and eradicates cancer stem cells, whilst leaving healthy cells alone, making it less toxic compared with standard treatment approaches," said Dr Kenyon. "Furthermore, our technology appears to be effective against more aggressive, less differentiated tumor types where few treatment options exist, and prognosis is poor, especially in the case of pancreatic and ovarian cancers. I look forward to advancing PRP to human studies where we can fully assess the clinical efficacy of PRP in a controlled setting."

Propanc plans to undertake a First-In-Human study in 30 to 40 advanced cancer patients suffering from solid tumors to determine a maximum tolerated dose for PRP treatment, followed by two proof of concept studies in pancreatic and ovarian cancers, 60 patients in each study, to confirm the clinical efficacy of PRP in the selected target therapeutic indications.

PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung, liver, uterine and skin cancers.

On September 29, 2022 aTyr Pharma, Inc. (Nasdaq: LIFE), a biotherapeutics company engaged in the discovery and development of first-in-class medicines from its proprietary tRNA synthetase platform, reported that the U.S. Patent and Trademark Office (USPTO) has provided a Notice of Allowance for a patent covering methods for the use of anti-neuropilin-2 (NRP2) antibodies (Press release, aTyr Pharma, SEP 29, 2022, View Source [SID1234621562]). The patent application No. 16/376,979 titled, "Compositions and methods comprising anti-NRP2 antibodies," covers the use of a series of antibodies targeting NRP2 for differentiated therapeutic applications in the areas of cancer and inflammation.

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NRP2 is a cell surface receptor that plays multiple roles in neurodevelopment, maintaining cellular plasticity, cell migration, lymphatic development and regulating inflammatory responses in normal physiology. The blocking antibodies that aTyr has developed target distinct domains of NRP2, including those interacting with semaphorins, VEGF and certain chemokines.

"We are pleased with the USPTO Notice of Allowance for this patent covering compositions and methods comprising anti-NRP2 antibodies, including our investigational new drug (IND) candidate ATYR2810, which is the first patent to be granted to our intellectual property estate for this program," said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr.

A Notice of Allowance is issued after the USPTO makes the determination that a patent should be granted from an application. A patent from the recently allowed application is expected to be issued in the coming months.

aTyr’s global patent estate includes over 220 issued or allowed patents owned or exclusively licensed by aTyr and its Hong Kong subsidiary, Pangu BioPharma Limited, developed over a decade of research and development activities. This patent estate highlights aTyr’s unique leadership position in this emerging area of biology. These patents encompassed important new therapeutic modalities which underpin the broad pipeline of novel therapeutics in active development at the company.

On September 29, 2022 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that data from a bioequivalence study for GFH009, its potent, highly selective, clinical-stage small molecule that inhibits cyclin-dependent kinase 9 (CDK9) (Press release, Sellas Life Sciences, SEP 29, 2022, View Source [SID1234621560]). In the ongoing Phase 1 clinical trial of GFH009 monotherapy in patients with relapsed/refractory hematologic conditions, including acute myeloid leukemia and lymphoma, GFH009 is administered intravenously as a solution. The bioequivalence study was performed to evaluate the effect of different formulations on GFH009’s preclinical pharmacokinetic (PK) profile. Dr. Dragan Cicic, MD, Senior Vice President, Clinical Development, of SELLAS, presented the findings at this year’s Meeting of the Society of Hematologic Oncology (SOHO) in a poster titled "Pharmacokinetics and Bioequivalence of Two Formulations of GFH009 Maleate Injection in Sprague Dawley Rats."

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The solution for GFH009 was originally developed with the pH of 4.5 (acidic). Human blood has a physiological pH of around 7.35 to 7.45. The closer a drug is to this physiological state, the less acidic and irritating it is for patients. In a four-week rat study, GFH009 was tested at 2.0 mg/kg, 4.0 mg/kg and 8.0 mg/kg. At 4.0 mg/kg, drug exposure approached efficacy, which formed the rationale for the dose selection for the presented PK study. Rats were randomly assigned to group one (pH 4.5) or group two (pH 6.0) and matched by sex and body weight. Each rat received a single dose of GFH009 (4.0 mg/kg) at pH 4.5 or pH 6.0 intravenously in the tail vein at a volume of 5.0 mL/kg. The PK profiles of both GFH009 formulations (pH 4.5 and pH 6.0) were found to be comparable, supporting the application of the pH 6.0 formulation in the ongoing Phase 1 clinical trial.

"At pH 6.0, GFH009 is closer to the physiological pH – thus, it is less acidic – and the drug’s behavior remains comparable to that at pH 4.5," said Dr. Cicic. "As a result, this study allowed us to explore a range of dosing strategies for patients, which helped with dose preparation and administration. The improved formulation also decreased the potential for the infusion reaction and made dosing more well-tolerated after multiple doses or long-time infusion."

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.

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.