On June 16, 2022 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage company developing disruptive therapeutics for the treatment of patients with cancer, reported the closing of its acquisition of Cancer Prevention Pharmaceuticals, Inc. (CPP), a private clinical stage company developing therapeutics to reduce the risk and recurrence of cancer and rare diseases, for a combination of stock and future milestone payments (Press release, Panbela Therapeutics, JUN 16, 2022, View Source [SID1234616044]).

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The combined entity will focus on maximizing its extensive pipeline addressing an estimated aggregate $5 billion market opportunity for the areas of initial focus: familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, colorectal cancer prevention and ovarian cancer.

"Closing this transaction achieves our goal of creating a diversified pipeline with an ability to hit multiple targets, four clinical stage assets, two of which are late-stage registration assets, thereby increasing the potential of the combined company," said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. "Together, our capabilities will have an even greater chance to help more patients. The addition of CPP is an excellent fit that we feel produces substantial shareholder value."

The closing of the merger follows the satisfaction of all customary closing conditions, including the unanimous approval by the boards of directors of each company and the stockholders of CPP.

About our Pipeline

The pipeline consists of assets currently in clinical trials with an initial focus on familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, neoadjuvant pancreatic cancer, colorectal cancer prevention and ovarian cancer. The combined development programs have a steady cadence of catalysts with programs ranging from pre-clinical to registration studies.

SBP-101

SBP-101 is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. The molecule has shown signals of tumor growth inhibition in clinical studies of US and Australian metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 14.6 months which is final, and an objective response rate (ORR) of 48%, both exceeding what is seen typically with the standard of care of gemcitabine + nab-paclitaxel suggesting potential complementary activity with the existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, SBP-101 has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the current Panbela sponsored clinical trial provides support for continued evaluation of SBP-101 in a randomized clinical trial. For more information, please visit View Source .

Flynpovi

Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism inhibiting polyamine synthesis and increase polyamine export and catabolism. In a Phase 3 clinical trial in patients with sporadic large bowel polyps, the combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Focusing on FAP patients with lower gastrointestinal tract anatomy in the recent Phase 3 trial comparing Flynpovi to single agent eflornithine and single agent sulindac, FAP patients with lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), Flynpovi showed statistically significant benefit compared to both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years. The safety profile for Flynpovi did not significantly differ from the single agents and supports the continued evaluation of Flynpovi for FAP.

CPP-1X

CPP-1X (eflornithine) is being developed as a single agent tablet or high dose power sachet for several indications including prevention of gastric cancer, treatment of neuroblastoma and recent onset Type 1 diabetes. Preclinical studies as well as Phase 1 or Phase 2 investigator-initiated trials suggest that CPP-1X treatment is well tolerated and has potential activity.

On June 16, 2022 Invectys, Inc. (Invectys), The University of Texas MD Anderson Cancer Center and the Cell Therapy Manufacturing Center (CTMC), a joint venture between MD Anderson and National Resilience, Inc., reported a strategic collaboration to jointly develop a reliable, compliant and scalable process for human leukocyte antigen (HLA)-G targeted chimeric antigen receptor (CAR) T cell therapy for solid tumors (Press release, Invectys, JUN 16, 2022, View Source [SID1234616043]).

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The collaboration will build upon the HLA-G platform pioneered by Invectys to advance novel CAR T cell therapies through preclinical development with CTMC into early-phase clinical studies at MD Anderson. The collaboration brings Invectys’ technology together with the cell therapy development and manufacturing expertise of CTMC and the clinical trials expertise of MD Anderson.

Uniting the complementary capabilities of Resilience and MD Anderson, CTMC was launched to accelerate the development and manufacturing of innovative cell therapies for patients with cancer.

"This agreement is truly about joining the strengths of each collaborator for the benefit of cancer patients," said Praveen Tyle, Ph.D., President and Chief Executive Officer of Invectys. "Invectys is a cancer immunotherapy company developing novel approaches to target HLA-G. With our combined expertise and shared goals, we can act quickly to advance impactful new cell therapies."

The HLA-G molecule is a powerful modulator of the human immune system that is normally found during pregnancy, when it acts to protect the fetus from rejection by the mother’s immune system. However, HLA-G is aberrantly expressed in cancer, making it an attractive tumor-specific antigen because the HLA-G tumor cells suppress a patient’s own innate immune responses. Invectys’ technology is designed to target and remove tumor cells that express HLA-G, thus reducing these immunosuppressive effects and thereby reactivating the patient’s own immune system.

"Immunotherapies have revolutionized the treatment landscape for cancer, but currently approved treatments are able to overcome immune suppression only in limited groups of patients," said Aung Naing, M.D., professor of Investigational Cancer Therapeutics at MD Anderson. "This novel HLA-G technology can revitalize immune cells by identifying and killing solid tumor cancer cells, thereby offering the potential to improve treatment outcomes for a wider group of cancer patients."

Together with researchers at Invectys, the CTMC team will work to develop a clinical-grade HLA-G targeted CAR T cell therapy for solid tumors that can be produced at scale. The collaboration will facilitate therapeutic development toward a Phase I clinical trial to be co-led by Naing and Samer Srour, M.D., assistant professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson.

"CTMC was established to accelerate patient impact by addressing the hurdles associated with the development and manufacturing of cell therapies," said Jason Bock, Ph.D., Chief Executive Officer of CTMC. "We are excited to work with the Invectys team and their unique technology to enable the anti-HLA-G CAR T cell therapy to reach its full potential, hopefully bringing an effective new treatment option to patients in need."

On June 16, 2022 INmune Bio, Inc. (NASDAQ: INMB) (the "Company"), a clinical-stage immunology company focused on developing treatments that harness the patient’s innate immune system to fight disease, reported that has been invited to present data on reversing resistance to HER2 targeted immunotherapy at the HER2 Targeted Therapy Summit in Boston (Press release, INmune Bio, JUN 16, 2022, View Source [SID1234616042]).

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Mucin 4 (MUC4), a glycoprotein on the cell surface of some epithelial cancers, is an easily measured biomarker in women with breast cancer (BC). MUC4 expression is upregulated by soluble tumor necrosis factor (sTNF) produced by the patient’s breast cancer cells. MUC4 expression predicts worse survival in women with HER2+ BC treated with trastuzumab (p≤0.04) and predicts resistance to trastuzumab and trastuzumab based antibody drug conjugates in pre-clinical models.

Dr. Roxana Schillaci of Instituto de Biología y Medicina Experimental in Buenos Aires and RJ Tesi, M.D. have been invited to give a special joint presentation at noon on June 16 entitled Resistance to Immunotherapy Caused by MUC4 Expression in HER2+ Tumors – Bench to Bedside. The presentation will present both the science driving MUC4-based resistance mechanisms and the translation of these pre-clinical studies to the clinic. A link to the presentation can be found HERE.

Dr. Schillaci, working in collaboration with INmune Bio, has shown in preclinical studies that INB03, a novel DN-TNF biologic that neutralizes soluble TNF, reverses MUC4 expression in HER2+ BC pre-clinical models to reestablish sensitivity to trastuzumab (traz) and trastuzumab ADC (TDM-1). In addition, women with MUC4+/HER2+ BC have a cold tumor with fewer tumor infiltrating lymphocytes (TILs) than women who do not express MUC4 (p=0.018). In a nude mouse model of MUC4+HER2+ BC, the combination of INB03+traz increased the number of activated NK cells (p=0.01) and anti-tumor macrophages (p=0.01) in the tumor microenvironment (TME) and showed anti-tumor macrophage function is more important than NK cell function in controlling tumor growth.

"We have identified three reversable resistance mechanisms in women with HER2+/MUC+ breast cancer – resistance to trastuzumab, resistance to tyrosine kinase inhibitors (eg: lapatinib and tucatinib) and a "cold" immunosuppressive TME. All three resistance mechanisms are driven by soluble TNF produced by the tumor and are reversed by neutralization of soluble TNF in the TME by INB03," said Dr. Schillaci.

"We estimate that resistance to immunotherapy occurs in about a third of women with high, low or ultra-low expression of HER2," added RJ Tesi M.D., CEO of INmune Bio. "As of result of the rapidly changing trastuzumab-based immunotherapy landscape, half of all women with breast cancer are at risk for trastuzmab resistance. MUC4 is a biomarker of resistance that can be determined by staining of patient’s breast cancer biopsy enabling a clinical team to prospectively adjust treatment to potentially improve outcome."

About INB03

INB03 is a DN-TNF inhibitor that neutralizes soluble TNF (sTNF) without affecting transmembrane TNF (tmTNF) or TNF receptors. Compared to currently available non-selective TNF inhibitors, INB03 preserves the immune response to cancer by decreasing immunosuppressive cells in the TME including TAM and MDSC while promoting recruitment of anti-tumor immune cells including cytolytic CD8+ lymphocytes, NK cells and anti-tumor macrophages. INB03 has completed an open label dose-escalation Phase I trial in patients with advanced cancer. In that trial, INB03 was found to be safe and well tolerated – no dose limiting toxicity was found. INB03 decreased blood biomarkers of inflammation in patients with advanced cancer. INMB is planning a Phase II trial that uses IN03 as part of combination therapy. More information about INB03 can be found by clicking here.

On June 16, 2022 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, reported the completion of enrollment in the first cohort of the ReSPECT-LM Phase 1/2a dose escalation clinical trial of Rhenium-186 NanoLiposome (186RNL) for the treatment of leptomeningeal metastases (LM) (Press release, Cytori Therapeutics, JUN 16, 2022, View Source [SID1234616040]).

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"We are pleased with initial response to the ReSPECT-LM trial by patients and physicians and the very early promising drug performance," said Norman LaFrance, M.D., Chief Medical Officer and SVP of Plus Therapeutics. "Patients seemed to tolerate 186RNL infusions and the drug circulated completely and rapidly throughout the cebrebrospinal fluid space. We intend to provide enrollment and complete clinical updates in the third quarter of 2022."

The investigational drug, 186RNL, is a proprietary nanoscale compound with a unique chelated radioisotope that is administered locally as a single dose via a conventional Ommaya reservoir. Rhenium-186 is a dual energy emitter (beta and gamma) with a short average path length for high precision, low dose rate that is safer for normal tissues, and high radiation density that overwhelms innate DNA repair mechanisms. The dual energy emission allows real time evaluation and monitoring of the 186RNL administration.

The ReSPECT-LM trial (NCT05034497) is a multicenter, sequential cohort, open-label, single dose, dose escalation Phase 1/2a study using a modified Fibonacci 3+3 study design. It will evaluate the maximum tolerated dose (MTD), maximum feasible dose (MFD), safety and efficacy of a single administration of 186RNL via intraventricular catheter for LM following standard surgical, radiation and/or chemotherapy treatment. The primary endpoints of the study are the incidence and severity of adverse events/serious adverse events and dose limiting toxicities. Secondary endpoints include overall response rate, duration of response, progression free survival and overall survival.

The ReSPECT-LM Phase 1/2a clinical trial follows preclinical studies in which tolerance to doses of 186RNL as high as 1,075 Gy was shown in animal models with LM with no observed significant toxicity. Treatment led to marked reduction in tumor burden in two animal models of LM.

In November 2021, the Company announced that the FDA granted Fast Track designation to 186RNL for the treatment of LM. Fast Track designation confers several benefits to the drug development program including 1) more frequent meetings with and written communication from FDA, 2) eligibility for Accelerated Approval and Priority Review, if relevant criteria are met, and 3) Rolling Review, which allows a drug company to submit completed sections of its New Drug Application (NDA) for review by FDA, rather than wait until every section of the NDA is completed before the entire application can be reviewed.

About Leptomeningeal Metastases (LM)

LM is a rare complication of cancer in which the disease spreads to the membranes (meninges) surrounding the brain and spinal cord. LM occurs in approximately 5% of people with cancer and is usually terminal with one-year and two-year survival of just 7% and 3% respectively. LM can originate from solid tumors, primary brain tumors, or hematological malignancies.

June 16, 2022 Akero Therapeutics, Inc. (Nasdaq: AKRO), a clinical-stage company developing transformational treatments for patients with serious metabolic diseases marked by high unmet medical need, reported two financing transactions (Press release, Akero Therapeutics, JUN 16, 2022, View Source [SID1234616039]). The first is a $25 million equity investment by Pfizer Inc. (NYSE: PFE) at $9.90 per share. The second is a term loan facility providing Akero with access to up to $100 million from Hercules Capital, Inc. (NYSE: HTGC), of which $10 million will be drawn at transaction close. Together with existing cash, proceeds will support Akero’s continued development of efruxifermin (EFX), a long-acting analog of fibroblast growth factor 21 (FGF21), including two ongoing Phase 2b clinical trials in patients with pre-cirrhotic and cirrhotic nonalcoholic steatohepatitis (NASH); manufacture of a drug product-device combination for use in Phase 3 clinical trials; and starting a Phase 3 clinical trial program. If the term loan is fully drawn, proceeds from these two transactions together with budget optimization efforts are expected to fund Akero’s current operating plan until the third quarter of 2024. This extends Akero’s previously announced cash guidance by a full year (from the third quarter of 2023 to the third quarter of 2024), two years beyond the anticipated readout of the HARMONY study in the third quarter of this year.

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"Pfizer has deep expertise and history in addressing health challenges that affect millions of patients around the world, including cardiometabolic diseases. We are honored and excited to have their confidence, collaboration and support," said Andrew Cheng, M.D. Ph.D., president and chief executive officer of Akero. "In addition, Hercules Capital has a rich history of investing in innovative biotechnology companies. We are very grateful for their significant partnership and support. With our existing cash on hand, we expect these two financings will extend our cash runway a full two years beyond our upcoming HARMONY readout, providing us the flexibility to optimize our capital structure to support the continued development of EFX."

Pfizer is investing in Akero through the Pfizer Breakthrough Growth Initiative (PBGI), which seeks to support biotechnology companies that share its commitment to delivering transformative therapies for patients in therapeutic areas consistent with Pfizer’s core areas of focus. Under the terms of the agreement, Akero has agreed to sell 2,525,252 shares to Pfizer at a price of $9.90 per share, for gross proceeds of $25 million. The shares of common stock were offered and sold to Pfizer in a registered direct offering conducted without an underwriter or placement agent. The offering is expected to close on or about June 17, 2022. Following the transaction, Pfizer will own approximately 6.7% of Akero’s outstanding common stock. As part of the transaction, Akero will establish a Scientific Advisory Board, with Pfizer appointing one member. Akero will maintain ownership and control of EFX, the rest of its pipeline, and Akero’s operations.

"EFX has quickly emerged as a promising potential NASH therapy, with a strong record of clinical trial data," said Jeff Pfefferkorn, Ph.D., Vice President of Discovery & Development, Internal Medicine Research Unit, Pfizer, who is expected to join Akero’s newly formed Scientific Advisory Board. "NASH is a priority therapeutic area for Pfizer due to the substantial global unmet medical need it represents, and we are excited to support Akero as it advances EFX towards a potential Phase 3 study."

The $100 million term loan facility is being provided by Hercules Capital, a leader in customized specialty financing for life science companies. Under the terms of the loan agreement, $10 million will be drawn at closing. An additional $10 million is immediately available to Akero at its sole discretion. Akero may draw an additional $35 million in two separate tranches upon achievement of near-term clinical and financial milestones. An additional $45 million may be drawn in a third tranche, subject to the approval of Hercules Capital. The loan bears an initial interest rate of 7.65% and adjusts with future changes in the prime rate. Akero will pay interest only for the first 24 months, extendable to 36 months on achievement of certain milestones. The loan matures 54 months from closing in December 2026. "We believe there is tremendous patient and clinical value in financing the development of potentially innovative treatments for NASH," said Cristy Barnes, Managing Director at Hercules Capital. "We’re excited to support Akero – both now and in the future – in its continued clinical development of EFX for the treatment of advanced NASH."