On September 28, 2022 Celltrion USA reported that the U.S. Food and Drug Administration (FDA) has approved Vegzelma (bevacizumab-adcd), a biosimilar to Avastin (bevacizumab)1, for the treatment of six types of cancer: metastatic colorectal cancer; recurrent or metastatic non-squamous non-small cell lung cancer (nsNSCLC); recurrent glioblastoma; metastatic renal cell carcinoma; persistent, recurrent, or metastatic cervical cancer; and epithelial ovarian, fallopian tube, or primary peritoneal cancer (Press release, Celltrion, SEP 28, 2022, View Source [SID1234621520]).

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"Biosimilars have been used in many disease areas including oncology, and have shown to be safe and effective while lowering the drug cost and increasing the access to more patients around the world," said Professor Claire Verschraegen, Director of the Division of Medical Oncology at the Ohio State University Comprehensive Cancer Center, Columbus, OH. "With the availability of biosimilars such as Vegzelma in the U.S., oncologists will have additional treatment options for patients across multiple cancer types."

The FDA approval of Vegzelma was based on the totality of evidence, including the pivotal phase III trial in patients with metastatic or recurrent nsNSCLC. Results showed that as a first-line treatment, Vegzelma is highly similar to the reference product in terms of efficacy, safety and pharmacokinetics.2

"The approval of Vegzelma is an important milestone in the U.S. which adds to our growing portfolio of oncology treatments and marks an important step forward in expanding access to cancer care," said Jaeik Shim, Chief Operating Officer at Celltrion USA. "As a leading force in the global biopharmaceutical industry, we look forward to working with payers and providers to make our product available to patients. With our high-quality and affordable biosimilar medicines, we plan to strengthen our presence in the U.S. and contribute to a more sustainable healthcare system for the future."

Vegzelma is Celltrion’s third oncology biosimilar approved for use in the U.S., following the approval of Truxima (rituximab-abbs) and Herzuma (trastuzumab-pkrb). Vegzelma was approved in the EU in August 2022 and UK and Japan in September 2022. Regulatory reviews are ongoing in additional countries.

– ENDS –

Notes to Editors:

About Vegzelma (CT-P16, biosimilar bevacizumab-adcd)2

Vegzelma is an anti-cancer monoclonal antibody treatment biosimilar to Avastin (bevacizumab). Vegzelma is a recombinant humanized monoclonal antibody which binds to vascular endothelial growth factor (VEGF), the key driver of vasculogenesis and angiogenesis, and thereby inhibits the binding of VEGF to its receptors Flt-1 (VEGFR-1), and kinase insert domain receptor (KDR) (VEGFR-2), on the surface of endothelial cells. In the U.S., Vegzelma is indicated for the treatment of patients with metastatic colorectal cancer (mCRC); recurrent or metastatic non-squamous non-small cell lung cancer (nsNSCLC); recurrent glioblastoma (GBM); metastatic renal cell carcinoma (mRCC); persistent, recurrent, or metastatic cervical cancer (CC); epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Vegzelma Important Safety Information3

Warnings and Precautions

Gastrointestinal Perforations and Fistula: Discontinue for gastrointestinal perforations, tracheoesophageal fistula, grade 4 fistula, or fistula formation involving any organ.

Surgery and Wound Healing Complications: In patients who experience wound healing complications during VEGZELMA treatment, withhold VEGZELMA until adequate wound healing. Withhold for at least 28 days prior to elective surgery. Do not administer VEGZELMA for at least 28 days following a major surgery, and until adequate wound healing. The safety of resumption of bevacizumab products after resolution of wound healing complication has not been established. Discontinue for wound healing complication of necrotizing fasciitis.

Hemorrhage: Severe or fatal hemorrhages have occurred. Do not administer for recent hemoptysis. Discontinue for Grade 3-4 hemorrhage.

Arterial Thromboembolic Events (ATE): Discontinue for severe ATE.

Venous Thromboembolic Events (VTE): Discontinue for Grade 4 VTE.

Hypertension: Monitor blood pressure and treat hypertension. Withhold if not medically controlled; resume once controlled. Discontinue for hypertensive crisis or hypertensive encephalopathy.

Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue.

Renal Injury and Proteinuria: Monitor urine protein. Discontinue for nephrotic syndrome. Withhold until less than 2 grams of protein in urine.

Infusion-Related Reactions: Decrease rate for infusion-related reactions. Discontinue for severe infusion-related reactions and administer medical therapy.

Embryo-Fetal Toxicity: May cause fetal harm. Advise females of potential risk to fetus and need for use of effective contraception.

Ovarian Failure: Advise females of the potential risk.

Congestive Heart Failure (CHF): Discontinue VEGZELMA in patients who develop CHF.

Pregnancy Warning

Based on findings from animal studies and their mechanism of action, bevacizumab products may cause fetal harm in pregnant women. Limited postmarketing reports describe cases of fetal malformations with use of bevacizumab products in pregnancy; however, these reports are insufficient to determine drug-associated risks. In animal reproduction studies, intravenous administration of bevacizumab to pregnant rabbits every 3 days during organogenesis at doses approximately 1 to 10 times the clinical dose of 10 mg/kg produced fetal resorptions, decreased maternal and fetal weight gain and multiple congenital malformations including corneal opacities and abnormal ossification of the skull and skeleton including limb and phalangeal defects. Furthermore, animal models link angiogenesis and VEGF and VEGFR2 to critical aspects of female reproduction, embryo-fetal development, and postnatal development. Advise pregnant women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Most Frequently Observed Adverse Reactions

Most common adverse reactions incidence (incidence > 10%) are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, hemorrhage, lacrimation disorder, back pain and exfoliative dermatitis.

On September 28, 2022 CLEARA Biotech B.V. ("Cleara" or the "Company"), a preclinical-stage biotechnology company focused on developing innovative, proprietary therapies for treating different pathologies of "scarred cellular" senescence, including late-stage cancer and chronic diseases, reported that it closed a $2.5 million seed financing round earlier in the year, led by Apollo Health Ventures, with participation from Curie Capital B.V., ROM Utrecht Region and Longevity Tech Fund (Press release, Cleara Biotech, SEP 28, 2022, View Source [SID1234621519]). The proceeds will be used to progress Cleara’s compounds toward clinical development and further build the Company’s developmental pipeline and management team.

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Cleara has optimized two lead developmental candidates, CL04177 and CL04183, that can eliminate scarred cancer cells found in several late-stage cancers and chronic diseases in humans. The Company is aiming to develop precision medicine tools that treat specific diseases with clear niche-directed, anti-senescent lead candidates, accompanied with associated biomarkers, around its FOXO4-based D-amino acid peptides and pipeline against subtypes of senescence.

As senescent cells impair tissue function, identifying how these cells avoid apoptosis allows for the prospective design of anti-senescence compounds and will be critical to address whether homeostasis can be restored. Cleara scientists identified FOXO4 as having the potential to sequester active, phosphorylated p53, preventing nuclear translocation and induction of apoptosis in scarred senescent and cancer cells. Senescent/scarred cells, as well as a range of chemo-resistant and/or metastatic cancers, share features and unique biomarkers that Cleara has identified, making them highly selective targets for CL04177/CL04183.

Designed and optimized based on an extensive (3D) structural, molecular and cellular understanding of cell scarring’s mechanism of action and how FOXO4 restrains this particular form of the cell guardian p53, both lead compounds potently counter viability of scarred cancer cells in 2D culture and 3D organoids, as well as strongly reduce the metastatic burden and infiltration in mouse in vivo models for metastatic colon cancer and triple-negative breast cancer. Furthermore, they show favorable pharmacokinetics and tissue distribution in mice, with an MTD that is well above their efficacious dose.

Additionally, Cleara has appointed Dr. Angelos Stergiou, New York-based SELLAS Life Sciences’ President and Chief Executive Officer, as its Board of Directors Chairman. Dr. Stergiou is a preeminent leader in the biotechnology industry with more than 20 years of experience in immuno-oncology, drug development and health economics, as well as deep expertise in finance and corporate governance.

"As Cleara’s vision is to develop novel, highly innovative approaches to combat life-threatening diseases, we look forward to further building the Company’s pipeline and advancing our preclinical studies," said Dr. Peter de Keizer, Managing Director and Scientific Founder, Cleara. "At the same time, Dr. Stergiou’s deep expertise in cancer drug development and impressive track record of building companies will be invaluable to use as we scale our preclinical and regulatory efforts in the U.S. and EU to enter the clinic by 2024."

"Cleara’s novel FOXO4-based treatment approach, which harnesses the unique attributes of utilizing biomarkers and ability to eliminate biomarker-positive scarred cells, specific subsets of senescence, has the potential to be a disruptive treatment paradigm for many high-unmet-need cancer patient populations," added Dr. Stergiou. "I look forward to working with the Board and management team as the Company continues to grow at such a pivotal time."

Dr. Marianne Mertens, Partner at Apollo Health Ventures, Cleara’s founding venture capital group and lead investor, concluded: "As we have worked closely with Cleara since its inception, playing a key role in the Company’s founding, Apollo Health Ventures has been extremely impressed with the progress achieved to date. We believe that the FOXO4-based approach, including the utilization of biomarkers, has great promise to develop safe and efficacious drugs in several diseases. We also look forward to benefiting from Dr. Stergiou’s biotech finance and operations knowledge, which will have an immediate and beneficial impact on our strategy to bring first- and/or best-in-class cancer drugs to patients."

On September 28, 2022 Gamida Cell Ltd. (Nasdaq: GMDA), the global leader in the development of NAM-enabled cell therapies for patients with hematologic and solid cancers and other serious diseases, reported that it has entered into a Commitment Letter with certain funds managed by Highbridge Capital Management, LLC ("Highbridge"), pursuant to which Highbridge has committed to provide a $25 million senior secured, convertible term loan (the "term loan") (Press release, Gamida Cell, SEP 28, 2022, View Source [SID1234621518]).

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The Commitment Letter does not represent a definitive credit facility and is subject to certain conditions, including the consummation of a Gamida Cell equity offering resulting in gross proceeds of not less than $20 million. The Commitment Letter provides, among other things, for: (i) a maturity date 24 months from the closing date for the term loan; and (ii) an annual interest rate of 7.50%, subject to increase to 12.00% upon the occurrence of certain events, payable on a quarterly basis, and, subject to certain conditions, payable in Gamida Cell’s ordinary shares which will be valued at 95% of the volume weighted average price over a period to be agreed upon. Obligations under the term loan will be secured by substantially all of our assets and the assets of our subsidiaries.

Subject to certain limitations, the lenders will be entitled to convert the term loan, together with a make-whole premium, equal to all accrued and unpaid, and remaining coupons due through the maturity date (the "make whole amount"), into Gamida Cell’s ordinary shares at a conversion price to be equal to a 35% premium to the arithmetic mean of the volume weighted average price of Gamida Cell’s ordinary shares for the three-trading day period commencing on September 28, 2022, which price is subject to adjustment in the event of ordinary share dividends, reclassifications and certain other fundamental transactions affecting the ordinary shares. Subject to certain conditions, the term loan will be immediately callable at 100% of the principal amount plus accrued and unpaid interest to the redemption date, plus the make whole amount, plus a redemption premium of 5%. Commencing four months after the closing date for the term loan, Gamida Cell will begin monthly repayments on the term loan of principal and accrued but unpaid interest on such amount with the make-whole amount. Such installment payments can be paid to Highbridge in either cash or stock.

Gamida Cell expects to pay certain fees and expenses of Highbridge and to enter into a registration rights agreement with Highbridge, pursuant to which Gamida Cell will be required to file a registration statement registering the resale by Highbridge of any ordinary shares of Gamida Cell issuable pursuant to the terms of the term loan within 30 days after the closing date for the term loan.

About Omidubicel

Omidubicel is an advanced cell therapy candidate developed as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant for patients with blood cancers. Omidubicel demonstrated a statistically significant reduction in time to neutrophil engraftment in comparison to standard umbilical cord blood in an international, multi-center, randomized Phase 3 study (NCT0273029) in patients with hematologic malignancies undergoing allogeneic bone marrow transplant. The Phase 3 study also showed reduced time to platelet engraftment, reduced infections and fewer days of hospitalization. One-year post-transplant data showed sustained clinical benefits with omidubicel as demonstrated by significant reduction in infectious complications as well as reduced non-relapse mortality and no significant increase in relapse rates nor increases in graft-versus-host-disease (GvHD) rates. Omidubicel is the first stem cell transplant donor source to receive Breakthrough Therapy Designation from the FDA and has also received Orphan Drug Designation in the US and EU.

Omidubicel is an investigational stem cell therapy candidate, and its safety and efficacy have not been established by the FDA or any other health authority. For more information about omidubicel, please visit View Source

About GDA-201

Gamida Cell applied the capabilities of its nicotinamide (NAM)-enabled cell expansion technology to develop GDA-201, an innate NK cell immunotherapy candidate for the potential treatment of hematologic and solid tumors in combination with standard of care antibody therapies. GDA-201, the lead candidate in the NAM-enabled NK cell pipeline, has demonstrated promising initial clinical study data. Preclinical studies have shown that GDA-201 may address key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs. Furthermore, these data suggest GDA-201 may improve antibody-dependent cellular cytotoxicity (ADCC) and tumor targeting of NK cells. There are approximately 40,000 patients with relapsed/refractory lymphoma in the US and EU, which is the patient population that will be studied in the currently ongoing GDA-201 Phase 1/2 clinical trial.

For more information about GDA-201, please visit View Source For more information on the Phase 1/2 clinical trial of GDA-201, please visit www.clinicaltrials.gov.

GDA-201 is an investigational cell therapy candidate, and its safety and efficacy have not been established by the FDA or any other health authority.

About NAM Technology

Our NAM-enabling technology is designed to enhance the number and functionality of targeted cells, enabling us to pursue a curative approach that moves beyond what is possible with existing therapies. Leveraging the unique properties of NAM (nicotinamide), we can expand and metabolically modulate multiple cell types — including stem cells and natural killer cells — with appropriate growth factors to maintain the cells’ active phenotype and enhance potency. Additionally, our NAM technology improves the metabolic fitness of cells, allowing for continued activity throughout the expansion process.

On September 28, 2022 Gamida Cell Ltd. (Nasdaq: GMDA), the global leader in the development of NAM-enabled cell therapies for patients with hematologic and solid cancers and other serious diseases, reported the pricing of a follow-on public offering of 12,905,000 of its ordinary shares at a public offering price of $1.55 per share for aggregate gross proceeds of $20 million, before deducting underwriting discounts and commissions and estimated offering expenses (Press release, Gamida Cell, SEP 28, 2022, View Source [SID1234621517]). In addition, Gamida Cell has granted the underwriters a 30-day option to purchase up to an additional 1,935,750 ordinary shares at the public offering price, less the underwriting discounts and commissions. The offering is expected to close on or about September 30, 2022, subject to satisfaction of customary closing conditions.

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Gamida Cell intends to use the net proceeds from this offering, together with its existing cash and cash equivalents and trading financial assets: for (i) commercial readiness activities to support potential launch of omidubicel, if approved; (ii) the continued clinical development of its NK product candidates, including GDA-201; and (iii) general corporate purposes, including general and administrative expenses and working capital.

Piper Sandler & Co. and JMP Securities, a Citizens Company, are acting as joint book-running managers for this offering.

A registration statement on Form S-3 (File No. 333-259472) relating to the ordinary shares has been filed with the Securities and Exchange Commission and declared effective on April 1, 2022. This offering will be made only by means of a prospectus supplement. Copies of the final prospectus supplement and the accompanying prospectus related to this offering may be obtained, when available, from: Piper Sandler & Co., 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, Attention: Prospectus Department, by telephone at (800) 747-3924 or by email at [email protected],or JMP Securities LLC, 600 Montgomery Street, Suite 1100, San Francisco, California 94111, Attention: Prospectus Department, by calling (415) 835-8985, or by e-mail at [email protected]. Investors may also obtain these documents at no cost by visiting the SEC’s website at View Source

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 jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On September 28, 2022 Oncotelic Therapeutics, Inc. ("Oncotelic" or the "Company") (OTCQB:OTLC), developer of treatments for rare and orphan indications, including Parkinson Disease, Pancreatic Cancer, and DIPG, reported that the Company will be presenting at the upcoming SITC (Free SITC Whitepaper) 37th Annual Meeting, held November 10-12, 2022, in Boston, MA (Press release, Oncotelic, SEP 28, 2022, View Source [SID1234621516]).

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Abstract Number: 599

Title: Mechanism of Action for OT-101 TGF-ß immunotherapy
Session Date: 11/10/2022 – 11/11/2022,
Presentation time: 9:00 am – 9:00 pm
"Pancreatic cancer is the fourth leading cause of cancer-related mortality with a 5-year survival rate of approximately 10%. Incidence of pancreatic cancer has been steadily increasing despite advances in immunotherapy." said Dr. Vuong Trieu, CEO Oncotelic. "Using deep learning we demonstrated a combinatory approach for treatment of pancreatic cancer leveraging on OT-101 as suppressor of TGF-β. We are initiating late-stage clinical trials around this program and are excite to work with leading thought leaders to bring OT-101 to patients".

About OT-101 Pancreatic Cancer Program

Pancreatic cancer is associated with the poorest prognosis of gastrointestinal cancers and is expected to become the second leading cause of cancer-related mortality in the USA by 2030. Globally, over 400,000 people die of pancreatic cancer each year. Pancreatic cancer is traditionally considered to be an immune-resistant disease. There is a lack of effector T cells, an abundance of myeloid-derived suppressor T cells, and a dearth of key immune effector and regulatory cells. This may be part of the reason why single-agent checkpoint inhibitors are not as effective in comparison to other diseases. Here is where breaking immune tolerance by inhibiting TGF-β with OT-101 will have a significant impact.

The P001 trial was an open-label, multicenter dose-escalation study to evaluate the safety and tolerability of OT-101 (TGF-β2-specific Phosphorothioate Antisense Oligodeoxynucleotide) in adult patients with advanced tumors known to overproduce TGF- β2, which are not or no longer amenable to established therapies. Of the 61 patients treated, 37 had advanced treatment failure pancreas cancer, a very difficult-to-treat cancer with an overall survival rate that is measured in months even with the best available chemotherapy regimens. Disease control (complete response (CR)), partial response (PR) or stable disease (SD)) was achieved in 19 of 35 evaluable pancreas cancer patients (54%). Among liver mets only patients, there are exceptional single-agent activity and survival. Patient 1006 was pushed to complete response (CR) and survived as far out as 77 mos. This patient failed multiple lines of therapies: (1) surgery: Whipple’s procedure, (2) 1st line: 5-FU/LV, Dose 425 mg/m2, (3) 2nd line: 5-FU/LV, Dose 2600 mg/m2/24hr, (4) 3rd line: Gemcitabine, Dose 1000 mg/m2/week, and (5) went on to OT-101with liver mets and complete response. Patient 1022 was pushed to stable disease ("SD") with overall survival of 40 months. This patient had also failed multiple lines of therapies: (1) surgery: Whipple’s procedure, (2) 1st line: radiation therapy (50 Gy), (3) 2nd line: 5FU, and (4) went on to OT-101 with liver mets and SD.