PASCAL BIOSCIENCES PLANS NEW DIRECTION TO INCLUDE CONTRACT RESEARCH

On June 14, 2022 Pascal Biosciences Inc. ("Pascal" or "the Company") (TSXV:PAS) (OTC:PSCBF) (FSE: 6PB-FF) reported a renewed and expanded emphasis on the consulting and contract research component of the business. Pascal has previously had success by providing resources to other biotech companies (Press release, Pascal Biosciences, JUN 14, 2022, View Source [SID1234615969]). In particular, the Company worked with SoRSE Technology last year, bringing over $600,000 into the company. Pascal scientists have, combined, over 80 years of experience in biotechnology projects and have been involved in the discovery, preclinical, and clinical development of drugs approved by the FDA. Our intent is to leverage this expertise to provide consulting and research services to customers with projects primarily in the post-discovery to Phase I period of development.

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"Drug development has long timelines and, unless new drug candidates are forthcoming, preclinical teams tend to become redundant once a drug enters clinical studies." stated CEO Dr. Brian Bapty. "By providing virtual preclinical services, Pascal can provide the direction, experience, and facilities to efficiently support multiple preclinical programs." As with the SoRSE contract, Pascal will provide shared expertise and infrastructure so Biotech clients benefit from economies of scale while limiting fixed costs.

Pascal is in process of updating the website to reflect these changes. Pascal will continue development of internal programs notably, for Acute Lymphoblastic Leukemia which is funded by an NIH Grant, and glioblastoma which will be supported by funds from operations.

A Study in Nature Communications Reports that NeoImmuneTech’s NT-I7 Enhances CAR-T Cell Expansion, Persistence and Anti-tumor Activity

On June 14, 2022 NeoImmuneTech, Inc. (NIT or "NeoImmuneTech"), a clinical-stage T cell-focused therapeutics company, reported that Nature Communications (Impact Factor: 14.92) published the results of an in vivo study combining the long-acting human IL-7, NT-I7, with chimeric antigen receptor (CAR) T cells directed against CD19+ B cell lymphoma and acute myeloid leukemia (Press release, NeoImmuneTech, JUN 14, 2022, View Source [SID1234615985]).

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The study led by Dr. DiPersio and his team at Washington University investigated the impact of NT-I7 on in vivo CAR-T cell expansion and anti-tumor response employing sophisticated models of B cell lymphoma or acute myeloid leukemia and an immune competent syngeneic model of acute promyelocytic leukemia. Utilizing these tools, the group tested whether NT-I7 could expand a less differentiated CAR-T product with improved durability and tumor killing abilities in multiple models of hematological cancer.

Over the past 10 years, CAR-T cell therapy has become routinely used to treat patients with refractory hematologic malignancies. Despite progress, long-lived memory responses and long-term in vivo persistence of CAR-T cells have yet to be consistently achieved to prevent tumor cell escape and clinical relapse.

In the study reported in Nature Communications, NT-I7 protected CD19-targeting CAR-T cells from cell death, enhancing their viability while promoting their expansion in the presence of CD19+ tumor cells. CAR-T cells expanded in the presence of NT-I7 were less differentiated but with equivalent effector cytokine secreting abilities. Treatment of tumor bearing mice with NT-I7 enhanced in vivo expansion and subsequent anti-tumor effects of CAR-T cells targeting CD19+ B cell lymphoma or CD33+ acute-myeloid leukemia. The combination of NT-I7 and CAR-T cells dramatically extended survival. Impressively, co-treatment of tumor bearing mice with NT-I7 reduced the minimum number of CAR-T cells needed to achieve a survival benefit by imparting increased tumor killing abilities to CAR-T cells on a per cell basis and expanding CAR-T cells in vivo. These studies provide compelling evidence that NT-I7 has the potential to enhance CAR-T therapy for the treatment of hematological diseases by promoting CAR-T anti-tumor activity, expansion and persistence.

Dr. Se Hwan Yang, Ph.D., President and Chief Executive Officer of NeoImmuneTech, Inc. said: "This Nature Communications article highlights the exciting properties of NT-I7 that can increase CAR T cells’ functionality and cytotoxicity. Those results demonstrate the broad applicability of NT-I7 for cellular therapy, in addition to its well-documented benefits as a long-acting human IL-7 that has the potential to amplify T cells across the subsets, boost the immune system, and enhance the anti-tumor response in people with hematologic malignancies and solid tumors."

This study presented in Nature Communications demonstrates the potential for NT-I7 to support impactful clinical use of multiple CAR-T therapies with improved safety and tolerability. Strategic combination of NT-I7 with CD19-targeting CAR-T cells is currently being tested as part of a multi-site clinical trial (NCT05075603) for the treatment of relapsed/refractory large B-cell lymphoma. At ASCO (Free ASCO Whitepaper) 2022, poster #239b presented the most advanced updates on this study (NIT-112) that aims to show if NT-I7 may increase expansion and persistence of CAR-T, leading to increased tumor response rate and improved clinical outcomes without safety concerns.

Reference: Kim, M.Y., Jayasinghe, R., Devenport, J.M. et al. A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity. Nat Commun 13, 3296 (2022). View Source

About chimeric antigen receptor (CAR-T) cells therapies

CAR-T cell therapy is a type of treatment in which a patient’s T cells (a type of immune system cell) are changed in the laboratory so they will attack specific cancer cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. Chimeric antigen receptor T-cell therapy is used to treat certain blood cancers, and it is being studied in the treatment of other types of cancer.

About NT-I7 (efineptakin alfa) (rhIL-7-hyFc)

NT-I7 (efineptakin alfa) is the only clinical-stage long-acting human IL-7, and is being developed in oncologic and immunologic indications, where T cell amplification and increased functionality may provide clinical benefit. IL-7 is a fundamental cytokine for naïve and memory T cell development and for sustaining immune response to chronic antigens (as in cancer) or foreign antigens (as in infectious diseases). NT-I7 exhibits favorable PK/PD and safety profiles, making it an ideal combination partner. NT-I7 is being studied in multiple clinical trials in solid tumors and as vaccine adjuvant. Studies are being planned for testing in hematologic malignancies, additional solid tumors and other immunology-focused indications.

Cogent Biosciences Announces Pricing of Upsized Public Offering of Shares of Common Stock and Pre-funded Warrants

On June 14, 2022 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported the pricing of an underwritten public offering of 15,169,698 shares of its common stock, offered at a public offering price of $8.25 per share (Press release, Cogent Biosciences, JUN 14, 2022, View Source [SID1234615953]). In addition, in lieu of issuing common stock to certain investors, Cogent is offering pre-funded warrants to purchase 3,030,302 shares of its common stock at a purchase price of $8.24 per pre-funded warrant, which equals the public offering price per share of the common stock less the $0.01 exercise price per share of each pre-funded warrant. The aggregate gross proceeds to Cogent from this offering are expected to be approximately $150 million, before deducting underwriting discounts and commissions and other estimated offering expenses, upsized from $125 million. In addition, Cogent has granted the underwriters a 30-day option to purchase up to an additional 2,730,000 shares of its common stock at the public offering price less underwriting discounts. All of the shares of common stock and pre-funded warrants in the offering are being sold by Cogent. The offering is expected to close on or about June 16, 2022, subject to customary closing conditions.

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Cogent intends to use the net proceeds from the offering for development, regulatory and commercial preparation activities relating to bezuclastinib and other product candidates, as well as for working capital and general corporate purposes.

Jefferies, Piper Sandler & Co. and Guggenheim Securities, LLC are acting as joint book-running managers for the offering. LifeSci Capital is also acting as lead manager for the offering.

The securities described above are being offered pursuant to a shelf registration statement (File No. 333-264773) filed with the Securities and Exchange Commission (SEC), which became effective on May 24, 2022.

A final prospectus supplement and accompanying base prospectus relating to and describing the terms of the offering will be filed with the SEC. The securities described above have not been qualified under any state blue sky laws. This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. The offering can be made only by means of a prospectus supplement and accompanying base prospectus, copies of which may be obtained at the SEC’s website at www.sec.gov, or by request to Jefferies LLC (Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, New York 10022; telephone: 877-821-7388; email: [email protected]); or Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, or by telephone at (800) 747-3924, or by email at [email protected]; or Guggenheim Securities, LLC: Attention: Equity Syndicate Department, 330 Madison, New York, New York 10017, by telephone at 212-518-9544, or by email at [email protected].

Propanc Biopharma’s PRP to Target 80 – 90% of Cancer Cases

On June 10, 2022 Propanc Biopharma, Inc. (OTCQB: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that the Company’s lead product candidate, PRP, targets solid tumors, which accounts for 80 – 90% of cancer cases, according to the National Cancer Institute (Press release, Propanc, JUN 14, 2022, View Source [SID1234615970]). Chief Scientific Officer and Co-Founder, Dr Julian Kenyon MD, MB, ChB, is leading research into a novel approach to prevent recurrence and metastasis from solid tumors using pancreatic proenzymes that target and eradicate cancer stem cells (CSCs), which are a small subpopulation of cells within tumors capable of self-renewal, differentiation and tumorigenicity when transplanted into an animal host. CSCs is the mechanism by which cancer is able to return and spread, even post standard treatments.

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Dr Kenyon explains that metastasis occurs because a program inside the cell, called the Epithelial-Mesenchymal Transition (EMT) is activated. The EMT is a biological process associated with wound healing and embryogenesis, but when associated with cancer, causes epithelial (organ originating) cancer cells to become invasive and stem cell like, features which then allow CSCs to spread and metastasize. PRP reverses the transition to a CSC and as such, reduces the metastatic potential of the tumor cells. Furthermore, traditional cancer therapies act on replicating cells, but not CSCs, so they rebuild the tumor mass and can migrate to start a new tumor in another organ. PRP stops CSCs so that a tumor loses the ability to generate new cells and the tumor disappears without the option to form a metastatic tumor elsewhere.

Dr Kenyon believes that PRP will be most effective against tumors which consist of a high percentage of CSCs, therefore less differentiated, more aggressive tumors which spread rapidly and often leads to a poor prognosis for the patient. These tumors are often a largely underserved patient population. Also, the EMT process which leads to cells transitioning to a mesenchymal (skeletal) state, implies that sarcomas, which is a cancer that originates in supportive and connective tissues such as bones, tendons, cartilage, muscle and fat, which are mesenchymal, could also be treated with PRP. Generally occurring in young adults, the most common sarcoma often develops as a painful mass on the bone. Sarcomas are particularly challenging tumors for which there are no effective treatments other than surgery in early stages. According to Dr Kenyon, these highly mesenchymal tumors would be likely to respond to PRP. This would be a breakthrough in the treatment of these types of tumors.

Dr Kenyon said, "Based on the mode of action, PRP targets 80 to 90% of all cancers, which is highly significant. Furthermore, sarcomas are a largely underserved patient treatment population with a poor prognosis for sufferers. I have reviewed early 19th century published clinical cases, when enzyme therapy was first proposed, including a 23 y/o female, with a large fibrosarcoma of the tongue, who was successfully treated, despite 3 unsuccessful surgeries due to recurrence. Over 100 years later, we have been able to elucidate a mechanism of action which explains why, and which tumors to target. Our scientific research over the last 15 years gives me great confidence about the potential of PRP as a breakthrough therapy for the treatment of metastatic cancer, which I believe will be tremendously impactful for humankind."

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.

J INTS BIO, Oral presentation of Preclinical results of its Novel Oral 4th Generation EGFR TKI ‘JIN-A02’ at the upcoming 2022 World Conference on Lung Cancer in Vienna, Austria

On June 14, 2022 J INTS BIO reported that it will be presenting the preclinical results of its NSCLC candidate ‘JIN-A02’ at the upcoming 2022 IASLC World Conference on Lung Cancer, to be held in Vienna, Austria from 6th to 9th August (Press release, J INTS BIO, JUN 14, 2022, View Source [SID1234615986]).

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‘JIN-A02’ is a novel orally administered 4th generation EGFR TKI that targets NSCLC cancers harboring C797S mutation. C797S is a mutation that occurs after the use of 3rd generation EGFR TKIs such as Osimertinib and Lazertinib, resulting in tumor resistance and disease progression.

According to J INTS BIO, ‘JIN-A02’ showed strong inhibitory activities against NSCLC cancer cell-lines harboring double and triple mutations with C797S mutations in in-vitro studies. In particular, ‘JIN-A02" showed robust inhibition against double mutations (Ex19Del/C797S or L858R/C797S), which with the increasing use of 3rd generation EGFR-TKIs as First Line therapy worldwide, will soon become the dominant mutations leading to resistance and disease progression.

In addition, ‘JIN-A02’ also effectively reduced tumor volume in a dose-dependent manner, compared to Osimertinib, in mouse model harboring EGFR Ex19Del/T790M/C797S triple mutation cancers and exhibited high brain penetrance with efficacy.

A company official added that ‘JIN-A02’ demonstrated a favorable safety profile with a low propensity for cardiotoxicity and did not show significant toxic effects such as weight loss and cytotoxicity in animal models at therapeutic dose levels. It is therefore expected to be a highly valued new drug in the armamentarium for the treatment of NSCLC.

Dr Anna Jo, CEO J INTS BIO, said: "We are determined to rapidly advance our novel NSCLC pipeline program, and to overcome the limitations of developing or approved treatments through rigorous R&D, so as to improve the outcomes of patients around the world who suffered from NSCLC with limited or no viable alternative treatments."