On August 15, 2022 Anixa Biosciences, Inc. (NASDAQ: ANIX) ("Anixa") a biotechnology company focused on the treatment and prevention of cancer and infectious diseases, reported that, in conjunction with its partner Moffitt Cancer Center, it has commenced treatment of the first patient in the clinical trial of its novel chimeric antigen receptor T-cell (CAR-T) therapy for ovarian cancer (Press release, Anixa Biosciences, AUG 15, 2022, View Source [SID1234618393]).

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The study is a dose-escalation Phase 1 trial to determine safety and the maximum tolerated dose of follicle stimulating hormone receptor T-cells and to preliminarily assess efficacy. The study is being conducted at Moffitt Cancer Center and will consist of up to 48 patients.

The CAR-T approach used for Anixa’s therapy is known as chimeric endocrine receptor T-cell (CER-T) since the target of the engineered T-cells is an endocrine receptor. While CAR-T therapy has shown efficacy in some hematological tumors, reproducing the same results with solid tumors, such as ovarian cancer, has proven challenging. One of the reasons for this difficulty is that effective CAR-T therapy needs a specific antigen to recognize that is only present on target cancer cells in order to avoid negatively affecting healthy cells. The CER-T therapy being evaluated in Anixa’s Phase 1 study differs from traditional CAR-T in that it targets the follicle stimulating hormone receptor (FSHR), which research indicates is exclusively expressed on ovarian cells in healthy adult females.

"We are pleased that the first patient has been treated in our ovarian cancer CAR-T clinical study," stated Amit Kumar, Ph.D., Chairman and CEO of Anixa Biosciences. "This is truly an exciting time for Anixa, as we have now begun treating patients in our second clinical trial. With our CAR-T study, we hope to determine whether our unique targeting approach will work in solid tumors—a difficult challenge for traditional CAR-T therapies."

Robert Wenham, M.D., MS, FACOG, FACS, the trial’s lead investigator and Chair of the Department of Gynecologic Oncology at Moffitt Cancer Center, added, "With limited treatment options for recurrent, chemo-resistant ovarian cancer, I am hopeful that this program can provide a unique opportunity to make a meaningful impact on patients of this devastating disease."

Jose R. Conejo-Garcia, M.D., Ph.D., Chair of the Department of Immunology at Moffitt Cancer Center and co-inventor of the CER-T technology, added, "It is exciting to see our novel FSHR-mediated CAR-T technology reaching patients, and if our unique CAR-T approach is successful, it could serve as a model for future targeted CAR-T therapies in other cancer types."

Dr. Conejo-Garcia and his research team developed the FSHR-mediated CAR-T technology when he was at the Wistar Institute where he contributed to report for the first time on the role of T-cell responses in the outcome of ovarian cancer patients. The clinical trial being conducted today is based on this pre-clinical work, originally published in Clinical Cancer Research. Anixa has an exclusive, world-wide license to this technology.

About Anixa’s CER-T Approach (Follicle Stimulating Hormone Receptor-Mediated CAR-T technology)
Anixa’s chimeric antigen receptor T-cell (CAR-T) technology approach is an autologous cell therapy comprised of engineered T-cells that target the follicle stimulating hormone receptor (FSHR). FSHR is found at immunologically relevant levels exclusively on the granulosa cells of the ovaries. Since the target is a hormone (chimeric endocrine) receptor, and the target-binding domain is derived from its natural ligand, this technology is known as CER-T (chimeric endocrine receptor T-cell) therapy, a new type of CAR-T.

On August 15, 2022 Addex Therapeutics (SIX and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, reported that its collaboration agreement with Indivior PLC (LON: INDV) for discovering and developing novel oral gamma-aminobutyric acid subtype B (GABAB) positive allosteric modulator (PAM) drug candidates has been extended until March 31, 2023 (Press release, Addex Therapeutics, AUG 15, 2022, View Source [SID1234618311]). As part of the amended agreement, Indivior will provide Addex with CHF 850,000 (approx. US $900,000) of additional research funding. The reserved indications, where Addex retains exclusive rights to develop its own independent GABAB PAM program, have also been expanded to include chronic cough, in addition to the rights to develop certain retained compounds for Charcot-Marie-Tooth type 1A neuropathy (CMT1A) and pain.

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"We have advanced the GABAB PAM program into the late stage of clinical candidate selection and are currently selecting compounds for entry into IND enabling studies for both Indivior’s program in substance use disorder and Addex’s independent programs for CMT1A, chronic cough and pain," said Mikhail Kalinichev, Head of Translational Science of Addex. "This additional research funding demonstrates the progress made to date in identifying novel GABAB PAM drug candidates and reflects the promise this mechanism of action has to bring significant benefit to the quality of life of patients".

"Indivior continues to be an important strategic partner for Addex as we continue to advance our preclinical portfolio towards the clinic and await the readout from the ADX71149 Phase 2 epilepsy study being conducted by our partner, Janssen Pharmaceuticals Inc., which is due to report top line data at the end of 2022," said Tim Dyer, CEO of Addex. "We also continue to advance discussions with potential partners across our portfolio and evaluate the future development path for dipraglurant, our mGlu5 NAM clinical program."

About GABAB Activation with PAM

Activation of gamma-aminobutyric acid subtype B (GABAB) receptor, a Family C class of GPCR, is clinically and commercially validated. The generic GABAB receptor agonist, baclofen, marketed for spasticity and some spinal cord injuries, has been shown to be efficacious in several other disease areas, including alcohol use disorder, CMT1A, chronic cough and pain. However, its wider use is limited due to a variety of side effects, rapid clearance and the development of tolerance. Novel, potent, selective and orally available positive allosteric modulators (PAMs) that potentiate GABA responses, rather than acting as orthosteric agonists at the GABAB receptor, like baclofen, are expected to deliver efficacy and have less adverse effects. Furthermore, PAMs only act when the natural ligand (GABA) activates the receptor, hence respecting the physiological cycle of activation, which is believed to explain why PAMs lead to less tolerance than direct agonists.

On August 15, 2022, Radius reported connection with the Merger, Parent, Purchaser, as the initial borrower immediately prior to the Merger, and the Company, as borrower after giving effect to the Merger, entered into a credit agreement (the "Credit Agreement") with OrbiMed Royalty & Credit Opportunities III, LP and OrbiMed Royalty & Credit Opportunities IV, LP, as lenders, and Wilmington Trust, National Association, as administrative agent, providing for a $350.0 million senior secured term facility (the "Term Loan") (Filing, 8-K, Radius, AUG 15, 2022, View Source [SID1234618343]). The proceeds of the Term Loan were used on the closing date under the Credit Agreement to finance the transactions contemplated by the Merger Agreement, to refinance certain existing indebtedness of the Company and to pay related fees and expenses.

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The Term Loan will mature on August 15, 2028. The Term Loan will start amortizing on the 37-month anniversary of the closing date, with equal monthly installments of principal due through the maturity date.

Borrowings under the Term Loan bear interest at a rate per annum equal to the greater of (a) 30-day average SOFR and (b) one-half percent (0.50%) per annum, in either case, plus the applicable margin of eight percent (8.00%) per annum ("Interest"). For the first twelve (12) months after the closing date, the Company will have the option to accrue up to one-half percent (0.50%) of the Interest as a payable in kind.

The Credit Agreement contains representations and warranties, covenants and events of default customary for agreements of this type.

Supplemental Indenture for Convertible Notes

In connection with the consummation of the Merger, the Company and Wilmington Trust, National Association, as trustee (the "Trustee"), entered into a Second Supplemental Indenture, dated as of August 15, 2022, which amends and supplements the Base Indenture, dated as of August 14, 2017, by and between the Company and the Trustee (the "Base Indenture"), as supplemented by the First Supplemental Indenture, dated as of August 14, 2017, by and between the Company and the Trustee (the "First Supplemental Indenture"), governing the Company’s 3.00% Convertible Senior Notes due 2024 (the "Notes") in the aggregate outstanding principal amount of approximately $193,000,000. The Second Supplemental Indenture was entered into to provide for a change in the conversion right of the Notes resulting from the Merger.

The Second Supplemental Indenture provides that, from and after the effective time of the Merger (the "Effective Time"), the right to convert each $1,000 principal amount of the Notes based on a number of Shares equal to the Conversion Rate (as defined in the First Supplemental Indenture) in effect immediately prior to the Merger will be changed into a right to convert such principal amount of Notes based on a number of units of reference property equal to the Conversion Rate consisting of (i) prior to the Milestone Payment Date (as defined in the CVR Agreement), $10.00 in cash and one (1) CVR, and (ii) after the occurrence of the Milestone Payment Date, $10.00 in cash plus the Milestone Payment Amount (as defined in the CVR Agreement) in cash.

The Second Supplemental Indenture also provides that the Company irrevocably elects to eliminate Cash Settlement and Combination Settlement (each as defined in the First Supplemental Indenture) and that its obligations to convert the Notes will be satisfied solely by Physical Settlement (as defined in the First Supplemental Indenture).

The foregoing description of the Base Indenture, the First Supplemental Indenture and the Second Supplemental Indenture does not purport to be complete and is subject to, and qualified in its entirety, by the full text of the Base Indenture and the First Supplemental Indenture, which were included as Exhibits 4.1 and 4.2, respectively, to the Company’s Current Report on Form 8-K, filed with the SEC on August 14, 2017, and is incorporated into this Item 1.01 of this Current Report on Form 8-K by reference, and the full text of the Second Supplemental Indenture, which is included as Exhibit 10.1 hereto, is incorporated herein by reference.

On August 15, 2022 Fusion Antibodies reported that it is delighted to be attending Antibody Engineering & Therapeutics (Press release, Fusion Antibodies, AUG 15, 2022, View Source [SID1234618359]).

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This event will be delivered in San Diego from 4-8th December 2022.

This is the #1 Antibody Engineering Conference for acceleratinf next generation antibosies to commercial success.

On Tuesday December 6th at 12:05pm, our CSO Dr Richard Buick will be delivering a scientific briefing on the following topic:

OptiMAL – A Novel Library and Mammalian Display Platform for Antibody Discovery
We present a novel synthetic antibody library based on the natural human repertoire, coupled to a powerful CHO cell mammalian display platform. This
library has been screened by a combination of MACS and FACS to select antibodies against the immune-oncology target PD-1.

Get in touch below to organise a meeting with one of the Fusion Antibodies team.

On August 15, 2022 Novartis reported that the Phase III CANOPY-A study evaluating adjuvant treatment with canakinumab (ACZ885), an inhibitor of interleukin-1beta (IL-1β), in adult patients with stages II-IIIA and IIIB (T>5cm N2) completely resected (R0) non-small cell lung cancer (NSCLC) did not meet its primary endpoint of disease-free survival (DFS) versus placebo1 (Press release, Novartis, AUG 15, 2022, View Source [SID1234618375]). No unexpected safety signals were observed.1 Findings from the trial will be presented at an upcoming medical meeting.

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"We made an investment in the CANOPY program based on signals of reduced lung cancer incidence and mortality observed in the CANTOS study. These positive signals supported the study of canakinumab as adjuvant treatment for early lung cancer," said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development, Novartis. "While we are disappointed CANOPY-A did not show the benefit we hoped for, every trial generates scientific evidence that supports future research and development, and we look forward to continuing to pursue new therapeutic options for people living with lung cancer, whose needs remain urgent and significant. We thank the patients and clinical investigators whose time and commitment made this research possible."

CANOPY-A is a Phase III, multicenter, randomized, double blind study that is evaluating the efficacy and safety of canakinumab as adjuvant treatment in patients with NSCLC stages II-IIIA and IIIB (T>5cm N2), per American Joint Committee on Cancer/The Union for International Cancer Control (AJCC/UICC) 8th edition staging, whose margins are free of cancer following surgery2. In the trial, 1,382 patients were randomized 1:1 to canakinumab, 200 mg subcutaneously every three weeks, or matching placebo for up to one year2. Patients completed standard-of-care adjuvant cisplatin-based chemotherapy and radiation therapy, if applicable, prior to randomization2.

About canakinumab (ACZ885)
Canakinumab is a human monoclonal antibody that binds with high affinity and selectivity to human IL-1β and inhibits IL-1β activity by blocking its interaction with its receptors3-5. By inhibiting IL-1β, preliminary evidence suggests that canakinumab may suppress Pro-Tumor Inflammation to 1) enhance anti-tumor immune response; 2) reduce tumor cell proliferation, survival and invasiveness; and 3) impair angiogenesis5. Pro-Tumor Inflammation enables tumor development by driving cancer-causing processes and suppressing anti-tumor immune responses6,7.

About the CANOPY program
Novartis launched the CANOPY study program after observing significantly lower than expected rates of lung cancer mortality among patients in the Phase III cardiovascular CANTOS trial. The CANTOS trial evaluated canakinumab as a secondary prevention measure for cardiovascular events in patients following a heart attack5,8. Patients in the CANTOS trial also were at high risk for inflammatory cancers like lung cancer due to advanced age, smoking history, and other clinical risk factors5,8. Based on these findings, Novartis launched three large-scale, randomized, Phase III clinical trials and a Phase II clinical trial to investigate canakinumab as a potential treatment option in NSCLC.

Novartis and lung cancer
Lung cancer is one of the most common cancers worldwide, accounting for more than 2 million new cases diagnosed each year9. More people die of lung cancer every year than any other cancer9. There are two main types of lung cancer—small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)10. NSCLC accounts for approximately 85% of lung cancer diagnoses11, and 30-55% of patients with early NSCLC develop recurrence despite resection12.

Novartis is committed to working with the scientific and medical communities to reimagine the treatment of lung cancer and pursue advances in medicine that could extend the survival of people living with lung cancer. Novartis is developing experimental therapies that block cancer growth; learning more about ways to activate the body’s immune system; increasing understanding of the relationship between chronic inflammation and tumor growth and progression; and exploring the potential for advanced nuclear medicine to fight the disease.