On June 6, 2022 Senhwa Biosciences, Inc. (TPEx: 6492), a drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and novel coronaviruses, reported that it has received written approval from the Human Research Ethics Committee (HREC), Australia to begin a Phase I study evaluating Senhwa’s Pidnarulex, the 2019 PCF-Pfizer Global Challenge Awards winner will be used in combination with Pfizer’s PARP inhibitor, Talazoparib (Talzenna), to explore potential therapy in patients with metastatic The study will be conducted by Peter MacCallum Cancer Centre (PMCC), Senhwa’s clinical partner in Melbourne, Australia (Press release, Senhwa Biosciences, JUN 6, 2022, View Source [SID1234615671]).

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This Phase I trial of Pidnarulex and Talazoparib will be mainly funded by the US Prostate Cancer Foundation (PCF) and Pfizer. Senhwa will provide supplies of their study drug, Pidnarulex, in addition to some specific funding for the study.

Pfizer’s Talazoparib, an oral PARP inhibitor (PARPi), received FDA’s approval in October 2018 for the treatment of adults with deleterious or suspected deleterious germline BRCA mutation–positive, HER2-negative locally advanced or metastatic breast cancer. While BRCA1/2 deficient tumor cells are responsive to PARPi treatments, the development of PARPi resistance is common.

In the previous Phase I trial conducted by CCTG, Senhwa’s Pidnarulex demonstrated clinically significant and persist benefits in patients with specific tumor biomarkers, such as BRCA1/2, and PALB2 mutations, and who had been exposed to platinum and other chemotherapeutics.

"Pidnarulex, alone, has shown efficacy in tumor cells resistant to PARPi in the preclinical studies. Therefore, we think Pidnarulex demonstrates great potential as an alternative treatment for prostate cancer patients who have acquired resistance to PARPi or other chemotherapies," said Dr. John Soong, Chief Medical Officer of Senhwa Biosciences.

Prostate Cancer is the second most lethal cancer for men in the United States. Although nearly 70% of patients can be cured with surgery, once the cancer has metastasized, almost all patients develop into castration-resistance, with a median survival time of less than two years.

About Pidanrulex (CX-5461)

Specific mutations within the Homologous Recombination (HR) pathway may be exploited by Pidnarulex through a synthetic lethality approach by targeting the DNA repair defects in Homologous Recombination Deficiency (HRD) tumors. Specifically, Pidnarulex is designed to stabilize DNA G-quadruplexes of cancer cells which leads to disruption of the cell’s replication fork. While acting in concert with HR pathway deficiencies, such as BRCA1/2 mutations, replication forks stall and cause DNA breaks, ultimately resulting in cancer cell death.

On June 6, 2022 Yumanity Therapeutics, Inc. ("Yumanity") (Nasdaq: YMTX), a clinical-stage biopharmaceutical company focused on the discovery and development of innovative, disease-modifying therapies for neurodegenerative diseases, reported it has entered into definitive agreements for two strategic transactions (Press release, Yumanity Therapeutics, JUN 6, 2022, View Source [SID1234615707]).

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The first definitive agreement is an asset purchase agreement for the sale of Yumanity’s lead clinical-stage product candidate, YTX-7739, as well as Yumanity’s unpartnered discovery-stage neuroscience product candidates and targets to Janssen Pharmaceutica NV ("Janssen"), part of the Janssen Pharmaceutical Companies of Johnson & Johnson, for $26 million in cash. In connection with the closing of the proposed transaction, Yumanity plans to distribute any remaining available cash proceeds from the sale to Yumanity stockholders via a one-time dividend, net of any amounts retained for outstanding obligations and net cash requirements associated with the proposed merger between Yumanity and Kineta, Inc. ("Kineta"). The amount of such dividend will depend on many factors and will not be determined until closer to the closing date.

Under the second definitive agreement, Kineta will become a wholly-owned subsidiary of Yumanity in an all-stock transaction, resulting in a combined publicly traded company re-named Kineta, Inc., that will focus on immuno-oncology and continue Yumanity’s ongoing research collaboration with Merck & Co. in amyotrophic lateral sclerosis and frontotemporal lobar dementia. Upon completion of the proposed merger, on a pro forma basis and based upon the number of Yumanity shares to be issued in the proposed merger, current Kineta stockholders are expected to own approximately 85% of the combined company and current Yumanity stockholders are expected to own approximately 15% of the combined company. The actual allocation will be subject to adjustment based on each company’s outstanding equity ownership and Yumanity’s net cash balance at the time of the closing of the proposed merger. The combined company expects to raise a concurrent private investment in public equity (the "PIPE financing") led by Growth & Value Development Inc.

"After evaluating Yumanity’s strategic alternatives, management and our Board of Directors believes that the proposed transactions are in the best interest of Yumanity’s stockholders," said Richard Peters, President and CEO of Yumanity. "We are excited that our lead clinical-stage neurology asset and unpartnered assets will continue to be developed and we are very enthusiastic about Kineta’s innovative oncology pipeline."

Kineta’s IND-ready, lead asset is KVA12.1, a potential best-in-class VISTA blocking immunotherapy to address the problem of immunosuppression in the tumor microenvironment. It is a fully human engineered IgG1 monoclonal antibody that was designed to bind to VISTA through a unique epitope. KVA12.1 may be an effective immunotherapy for many types of cancer including NSCLC (lung), colorectal, renal cell carcinoma, head and neck, and ovarian. These initial target indications represent a significant unmet medical need with a large worldwide commercial opportunity for KVA12.1. Kineta is also developing fully human antibodies that target CD27 and CD24. These immunotherapies are engineered to address the problems of exhausted T cells and immunologically silent tumors.

"The proposed merger with Yumanity is a unique opportunity for Kineta to build a leading public immuno-oncology focused company with a diversified pipeline of new treatments for cancer patients," said Shawn Iadonato, Ph.D., CEO of Kineta. "Kineta has demonstrated expertise in developing novel immunotherapies that will enable us to advance our lead programs towards multiple milestones over the next 18 months."

The Yumanity Board of Directors has unanimously approved both definitive agreements. The Kineta Board of Directors has unanimously approved the definitive merger agreement with Yumanity. The two transactions are expected to close in the second half of 2022, subject to customary closing conditions, including approval of both transactions by the stockholders of Yumanity.

On June 6, 2022 Enterome, a clinical stage biopharmaceutical company developing first-in-class immunomodulatory drugs based on its bacterial Mimicry drug discovery platform, reported proof-of-concept immune response data and first clinical data from its Phase 1/2 clinical trial of EO2401 in combination with an immune checkpoint inhibitor (nivolumab, Opdivo) in patients with non-resectable adrenocortical carcinomas (ACC), treated with at least one line (but not more than two prior lines of systemic therapy), or without prior systemic therapy for advanced/metastatic disease (SPENCER trial, EOADR1-19, NCT04116658) (Press release, Enterome, JUN 6, 2022, View Source [SID1234615606]). The data1 were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, on June 4, 2022 in Chicago and virtually.

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EO2401 is Enterome’s first-in-class off-the-shelf OncoMimics cancer immunotherapy. It combines three OncoMimics peptides that closely mimic IL13Ra2, BIRC5 and FOXM1, all of which are known driver antigens present on aggressive solid tumors. In addition, EO2401 contains a CD4 helper peptide UCP2. Enterome selected these OncoMimics peptides using its Mimicry platform, which applies best-in-class biocomputational tools and bioassays to identify novel therapeutics from its proprietary database of 20+ million bioactive gut microbiome peptides and proteins.

Key highlights from the EO2401 poster presentation covering the Phase 1/2 SPENCER trial were:

Proof-of-concept immune response data

Immune monitoring of Cohort 2a demonstrates the ability of microbiome-derived peptides to induce a strong Tc1- skewed CD8+ T cell response with strong cross-reactivity against human selected tumor associated antigens.

The level of the specific CD8+ T cell immune responses against the microbiome-derived peptides comprising EO2401 were also found to correlate with clinical outcome (objective responses and progression-free survival).

Promising clinical outcome in sub-group of patients

The combination of EO2401 plus nivolumab was evaluated:

in patients with previously treated ACC (Cohort 2a, n=26) and
in patients who received no prior systemic therapy for advanced/metastatic disease (Cohort 2b, n=7)
Cohort 2a – group of patients showing benefit in objective tumor responses and time to progression

Analysis of Cohort 2a identified patients with clearly different efficacy outcomes, with one group showing benefit in objective tumor responses and time to progression, and another group with short progression-free survival (PFS) and short survival.

To refine the population for expansion in a randomized Phase 2 trial, different laboratory and clinical parameters were investigated as possible selection criteria.

No correlation was found between clinical outcome and tumor mutational burden, MSI-status, PD-L1 expression, serum cytokines/chemokines, or hormonal levels. However, the study found that patients in Cohort 2a who fulfilled the criteria of having received prior mitotane treatment, ECOG ≤ 1, ACC primary diagnosis > 9 months, max lesion size ≤ 125 mm, ≤ 3 organs involved, reduced lymphocytes ≤ grade 1 (n=14), demonstrated a clinical benefit vs patients not fulfilling these criteria (n=12), as follows:

Objective response rates (ORR) – 28.6% (95% CI 8.4; 58.1) vs 0% (95% CI 0.0; 26.5)
Disease control rates (DCR) – 64.3% (95% CI 35.1; 87.8) vs 3% (95% CI 0.2; 38.5)
Median progression-fee survival (PFS) – 3.9 months (95% CI 1.9; 9.2) vs 6 months (95% CI 0.5; 1.9)
Median survival – 13.0 months (95% CI 11.3; not evaluated) vs 1 months (95% CI 1.5; 7.4)

Cohort 2b – further follow up to be conducted

The clinical responses to EO2401 plus nivolumab observed in patients in Cohort 2b showed no benefit over the results from all patients in Cohort 2a, and further follow-up will be conducted.

Safety

The combination of EO2401, administered sub-cutaneously with the adjuvant Montanide ISA 51 VG, with nivolumab was well tolerated. The safety profile was consistent with the profile of nivolumab monotherapy, except the addition of local administration site reactions (occurring in 21% of patients).

Dr. Eric Baudin, Associate Professor and Head of the Endocrine Oncology Unit at the Institut Gustave Roussy (Villejuif, France) commented, "There has been no significant innovation in the treatment of advanced adrenal tumors and patients with this rare group of diseases are desperately in need of new effective therapies especially at relapse after first-line therapy. If confirmed, EO2401 in combination with nivolumab, represents the most promising therapy of the last three decades in this ultra rare cancer. I am pleased to be participating in this trial and to move forward into a randomized Phase 2 trial in this underserved patient population."

Dr. Jan Fagerberg, Chief Medical Officer of Enterome said, "The data presented at ASCO (Free ASCO Whitepaper) for EO2401 in combination with nivolumab are very encouraging, with strong immune responses correlating to clinical outcome in patients having been previously treated for adrenocortical carcinoma. We are also pleased to have been able to define a set of clinical selection criteria that will enable us to refine a patient population for expansion in a Phase 2 randomized trial. We are on track to start this new trial in the coming months and look forward to the results in due course."

EO2401 in recurrent glioblastoma

At ASCO (Free ASCO Whitepaper), and separately announced today, Enterome presented the first clinical data from its Phase 1/2 clinical trials of EO2401 in combination with nivolumab +/- bevacizumab for the treatment of patients with recurrent glioblastoma (the ROSALIE trial, EOGMB1-18). View press release here.

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About SPENCER

The SPENCER trial (EOADR1-19, NCT04187404) is a multicenter, open-label, Phase 1/2 study assessing the safety, tolerability, immunogenicity and preliminary efficacy of EO2401 in combination with the immune checkpoint inhibitor nivolumab in patients with adrenal tumors (adrenocortical carcinoma [ACC] and metastatic pheochromocytoma/paraganglioma [MPP]). The trial is expected to enrol at least 100 patients at clinical sites in Europe and the US.

On June 6, 2022 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company developing the next generation of therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported a trial-in-progress poster describing the study outline of its Phase 1b clinical trial of PH-762, a self-delivering RNAi targeting PD-1, for the treatment of advanced melanoma at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, which is being held June 3-7, 2022 in Chicago, IL (Press release, Phio Pharmaceuticals, JUN 6, 2022, View Source [SID1234615623]).

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Immunotherapy with antibodies targeting immune checkpoints, such as PD-1, has shown significant benefit in late stage melanoma patients. However, further improvements in therapeutic options are still needed. Treatment given as a first step prior to surgery, or neoadjuvant treatment, and local intratumoral (IT) injection are two alternative approaches for improving the outcome of immunotherapy for melanoma patients.

"We are pleased to share the details for the ongoing clinical trial of our lead product, PH-762. As the first-in-human study for an INTASYL immunotherapy compound, the initiation of this study earlier this year marks an important milestone for our broader pipeline and platform," said Dr. Simon Fricker, Phio’s VP of Research and Development. "Neoadjuvant therapy may stimulate significant responses that appear to be associated with a decrease in the risk of relapse after surgery. As there is currently no neoadjuvant standard of care for resectable advanced melanoma patients, neoadjuvant treatment with PH-762 provides an alternative therapeutic option to treat these patients."

IT administration of PH-762 to the tumor can stimulate a local immune response in the tumor microenvironment by silencing PD-1 and generating an immune response in distant untreated tumors. Studies conducted by the Company have shown potent silencing of PD-1 and a robust, dose-dependent inhibition of tumor growth. Further, IT injection of PH-762 also has the potential to minimize systemic effects and off-target toxicity, which has been seen with the use of antibodies.

The poster presented at ASCO (Free ASCO Whitepaper) outlines the design of the Phase 1b study with PH-762 for the treatment of patients with advanced melanoma. The clinical study is being conducted at the Gustave Roussy Institute, one of the largest cancer centers in Europe. The purpose of this study is three-fold: to evaluate the safety and pharmacokinetics of neoadjuvant use of PH-762 administered by IT injection in subjects with resectable advanced melanoma; to determine the recommended Phase 2 dose; and to determine the potential immunologic and pathologic tumor responses. Study treatment will feature a dose escalation of once weekly IT injections of PH-762 for four weeks prior to surgical excision of tumor lesion(s) after treatment with PH-762. Up to five dose levels will be tested in a serial fashion in cohorts of three or more subjects. A Bayesian optimal interval (BOIN) design will be employed to evaluate escalating doses of PH-762 to determine the maximum tolerated dose level and the dose of PH-762 will be normalized to tumor volume to ensure an equivalent local dose (tumor tissue concentration). Tumor changes will be evaluated per RECIST criteria, adapted for use with IT therapy, and by pathological response.

The poster being presented at ASCO (Free ASCO Whitepaper), titled, "A First-in-Human, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of Neoadjuvant Use of PH-762 Administered Intratumorally in Subjects with Advanced Melanoma" will be made available on the "Investors – Events and Presentations" section of the Company’s website (click here).

About PH-762

PH-762 activates immune cells to better recognize and kill cancer cells. It does so by reducing the expression of PD-1, a clinically validated target for immunotherapy. PD-1 is expressed by T cells and prevents them from killing cancer cells. When PH-762 reduces PD-1 expression, the "brakes" on the immune system are released and activates the T cells to kill the cancer cells. PH-762 is being developed as a standalone drug therapy with local IT administration to a tumor. In addition, it is also being developed as a critical component of cellular immunotherapy, more specifically to improve tumor cell killing capability of adoptively transferred tumor infiltrating lymphocyte (TIL) therapy.

On June 6, 2022 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for people living with cancer, reported an update from an interim analysis of its international Phase 2 RAMP 201 trial evaluating VS-6766 ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC), regardless of KRAS status (Press release, Verastem, JUN 6, 2022, View Source [SID1234615639]).

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Verastem recently completed a planned interim analysis of its RAMP 201 trial with the goal of selecting a go forward treatment regimen of either VS-6766 monotherapy or VS-6766 in combination with defactinib. The analysis indicated encouraging efficacy results with confirmed responses by independent review in patients treated with VS-6766 monotherapy and patients treated with VS-6766 in combination with defactinib. The findings also include confirmed responses by independent review in both KRAS mutant and KRAS wild-type LGSOC. To date, there have been no additional safety signals with a continued favorable safety profile in both the monotherapy and combination treatment arms with approximately 6% of patients discontinuing due to adverse events.

With a substantial majority (approximately 80%) of patients remaining on study treatment with a median duration of follow-up of four months, the Company has concluded that the data from the interim analysis are not mature enough to make a final decision on the go forward treatment regimen at this time and the trial will continue with all four cohorts (VS-6766 ± defactinib in KRAS mutant and KRAS wild type patient populations).

"We are encouraged by the positive anti-tumor activity that we have seen to date in the RAMP 201 trial in patients with both KRAS mutant and KRAS wild-type tumors. We look forward to evaluating a more mature data set and expect to provide an update on progress once the go forward treatment regimen has been determined," said Brian Stuglik, Chief Executive Officer, Verastem Oncology. "This interim analysis adds to our optimism about the potential for VS-6766 with or without defactinib and our commitment to advancing the first new treatment specifically developed and approved for women with low-grade serous ovarian cancer where a high medical need remains."

The Company plans to complete enrollment of all four cohorts of the trial in the second half of this year. Each cohort is expected to have approximately 36 patients for a total of 144 patients.

Both VS-6766 and defactinib are in late-stage development and the combination has received Breakthrough Therapy Designation by the U.S. Food and Drug Administration for the treatment of all patients with recurrent low-grade serous ovarian cancer regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.

About the VS-6766/Defactinib Combination

VS-6766 is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. In contrast to currently available MEK inhibitors, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The combination of VS-6766 and FAK inhibitor, defactinib provides RAF/MEK vertical blockade and FAK parallel inhibition to overcome key resistance mechanisms. Both VS-6766 and defactinib are in late-stage development.

Verastem Oncology is conducting Phase 2 registration-directed trials of VS-6766 alone and with defactinib in patients with recurrent LGSOC and in patients with recurrent KRAS G12V-mutant NSCLC as part of its RAMP (Raf And Mek Program) clinical trials, RAMP 201 and RAMP 202, respectively (www.ramp201study.com and www.ramp202study.com). Verastem Oncology has also established clinical collaborations with Amgen, Inc. and Mirati Therapeutics, Inc. to evaluate LUMAKRAS (sotorasib) and adagrasib in combination with VS-6766 in KRAS G12C-mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively.

About Low-Grade Serous Ovarian Cancer

Low-grade serous ovarian cancer is a highly recurrent, chemotherapy-resistant cancer, associated with slow tumor growth and high mortality rate.1 Approximately 6,000 women in the U.S. and 80,000 worldwide are living with this disease. Mutations in the KRAS gene are present in 35-57% cases of LGSOC.2 LGSOC is most often diagnosed in women between the ages of 45-55 years and has a median survival of approximately ten years.2 The majority of patients experience severe pain and complications as the disease progresses. Chemotherapy is the standard of care for this disease, with limited treatment options currently available.2