On December 14, 2021 Geron Corporation (Nasdaq: GERN), a late-stage biopharmaceutical company focused on the development and commercialization of treatments for hematologic malignancies, reported three poster presentations related to imetelstat, the Company’s first in class telomerase inhibitor, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Geron, DEC 14, 2021, View Source [SID1234597146]). The posters are available at www.geron.com/r-d/publications.

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"The posters for this year’s ASH (Free ASH Whitepaper) Meeting highlight our ongoing Phase 3 development of imetelstat in lower risk MDS and refractory MF, as well as exploratory work in new indications to maximize the potential value of imetelstat," said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. "We believe the unique telomerase inhibition MOA of imetelstat has the potential to transform the standard of care in hematologic malignancies."

Clinical Posters

Lower Risk Myelodysplastic Syndromes (MDS)

Abstract Title: On-Target Activity of Imetelstat Correlates with Clinical Benefits, Including Overall Survival (OS), in Heavily Transfused Non-Del(5q) Lower Risk MDS (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs) Abstract #2598

The poster reports new analyses to assess the correlation between imetelstat’s inhibition of telomerase with the efficacy and safety data from the IMerge Phase 2 clinical trial. These correlative analyses indicating that patients who achieved optimal pharmacodynamic (PD) effect achieved higher rates of red blood cell transfusion independence (RBC-TI), longer RBC-TI and a trend toward improved overall survival. Importantly, these patients did not have higher rates of Grade 3+ neutropenia, thrombocytopenia or liver function elevations compared to patients who did not achieve optimal PD effect.

These data provide further evidence for the on-target mechanism of action (MOA) of imetelstat through telomerase inhibition and links imetelstat’s on-target activity with clinical benefits.

To confirm these and other results from IMerge Phase 2, the Company is conducting a double-blind, randomized, placebo-controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 170 transfusion dependent patients with Low or Intermediate-1 risk myelodysplastic syndromes (MDS), also referred to as lower risk MDS, who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The primary endpoint is the rate of RBC-TI for any consecutive period of eight weeks or longer, or 8-week RBC-TI rate. Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks, or 24-week RBC-TI rate, and the rate of hematologic improvement-erythroid (HI-E), defined as a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden.

IMerge Phase 3 is fully enrolled and patient enrollment has been closed. Based on current planning assumptions, the Company expects top-line results from IMerge Phase 3 in early January 2023.

Refractory Myelofibrosis (MF)

Abstract Title: A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat Versus Best Available Therapy (BAT) in Patients with Intermediate-2 (Int-2) or High-risk Myelofibrosis (MF) Refractory to Janus Kinase Inhibitor (JAKi) Abstract #1503 Trials in Progress

IMpactMF is an open label, randomized, controlled Phase 3 clinical trial with registrational intent. The trial is planned to enroll approximately 320 patients with Intermediate-2 or High-risk myelofibrosis who are refractory to prior treatment with a JAK inhibitor, also referred to as refractory MF. Patients will be randomized to receive either imetelstat or best available therapy. The primary endpoint is overall survival (OS). Key secondary endpoints include symptom response, spleen response, progression free survival, complete response, partial response, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes.

IMpactMF is currently enrolling patients. For further information about IMpactMF, including enrollment criteria, locations and current status, visit ClinicalTrials.gov/NCT04576156.

Pre-Clinical Poster – Pediatric Acute Myeloid Leukemia

Abstract Title: Imetelstat Significantly Reduces Leukemia Stem Cells in Patient-Derived Xenograft Models of Pediatric AML Abstract #3352

Acute myeloid leukemia (AML) is the deadliest malignancy in children. To improve survival in pediatric AML, novel targeted therapies and other alternative treatment methods are needed. Due to the significant unmet medical need in this disease, the use of imetelstat was evaluated to determine whether the drug 1) has anti-leukemia activity and 2) could be used as a therapeutic for pediatric AML.

The poster describes results from pre-clinical studies of imetelstat in pediatric AML cell lines (in vitro studies) and patient derived (PDX) mouse models (in vivo studies). The efficacy of imetelstat either as a single agent or in combination with chemotherapy or azacitidine was also evaluated. In cell line experiments, imetelstat treatment resulted in cell apoptosis/death of leukemia stem cells (LSCs) in a time- and dose-dependent manner and with minimal effect on normal bone marrow samples. In the in vivo studies, imetelstat treatment reduced LSC numbers and prolonged survival in mice. Observations of prolonged survival in mice were also seen when combining imetelstat with chemotherapy or azacitidine.

These data suggest imetelstat may represent an effective therapeutic strategy to target the LSC population in pediatric AML patients.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from Phase 2 clinical trials provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.

On December 14, 2021 Legend Biotech Corporation (NASDAQ: LEGN) ("Legend Biotech"), a global clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and other indications, reported that it intends to offer and sell $300.0 million of American Depositary Shares ("ADSs"), each representing two ordinary shares, in an underwritten public offering. All ADSs to be sold in the proposed offering will be offered by Legend Biotech (Press release, Legend Biotech, DEC 14, 2021, View Source [SID1234597145]). Legend Biotech also intends to grant the underwriters a 30-day option to purchase up to an additional $45.0 million of ADSs sold in the public offering at the public offering price, less underwriting discounts and commissions. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed or the actual size or terms of the offering.

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Morgan Stanley, J.P. Morgan, Jefferies, Piper Sandler & Co. and Barclays are serving as joint book-running managers for the offering. BTIG is serving as a co-manager for the offering.

The ADSs are being offered by Legend Biotech pursuant to an effective shelf registration statement that was previously filed with the Securities and Exchange Commission ("SEC"). The offering is being made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. A copy of the preliminary prospectus supplement can be obtained, when available, from Morgan Stanley & Co. LLC, 180 Varick Street, New York, NY 10014, Attention: Prospectus Department, or by telephone at (866) 718-1649; J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at 866-803-9204 or by email at [email protected]; Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by email at [email protected] or by phone at (877) 821-7388; Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, or by email at [email protected] or by telephone at 1-800-747-3924; or Barclays Capital Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717 or by email at [email protected] or by telephone at (888) 603-5847.

This press release does not constitute an offer to sell or the solicitation of an offer to buy securities, and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction.

On December 14, 2021 Prestige BioPharma and Dr. Reddy’s Laboratories Ltd. (BSE: 500124, NSE: DRREDDY, NYSE: RDY, NSEIFSC: DRREDDY, hereafter referred to as "Dr. Reddy’s") reported that the two companies have entered into a binding agreement for an exclusive partnership for the supply and commercialization of Prestige BioPharma’s proposed trastuzumab biosimilar in select countries in Latin America and Southeast Asia (Press release, Prestige BioPharma, DEC 14, 2021, View Source [SID1234597141]).

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Prestige BioPharma’s trastuzumab (HD201) is a proposed biosimilar for the treatment of HER2 +ve breast and metastatic gastric cancer. Trastuzumab targets human epidermal growth factor 2 (HER2). In some types of cancer cells, HER2 is overexpressed and stimulates the growth of the cancer cells. Trastuzumab works by selectively binding to HER2, thereby stopping the growth of these cancer cells.

The license agreement grants Dr. Reddy’s the exclusive rights to commercialize the proposed biosimilar in select countries in Latin America and Southeast Asia. Under this partnership, Prestige BioPharma will be responsible for sustainable commercial supply of HD201 from its manufacturing facilities in Osong, South Korea, while Dr. Reddy’s will be responsible for local registrations, marketing and sales in the licensed territories.

Lisa S. Park, CEO of Prestige BioPharma, commented: "We are delighted to establish a partnership with Dr. Reddy’s for key Latin American and Southeast Asian markets. Dr. Reddy’s is the ideal partner to commercialize our lead biosimilar in these territories. With this collaboration, we look forward to further strengthening the value of our biosimilar programs in global markets."

M.V. Ramana, CEO – Branded Markets (India & Emerging Markets), Dr. Reddy’s, said: "In keeping with our purpose of accelerating access to affordable and innovative medicines, we are happy to bring this life-saving drug to patients in need. Our partnership with Prestige BioPharma will help us combine their established expertise in the area of biosimilars with our commercial strengths and growth ambition in these markets. This is in line with our stated intention to create a portfolio of oncology products and expand our biosimilar offerings in Emerging Markets."

On December 14, 2021 BostonGene Corporation and NEC Corporation (NEC; TSE: 6701) reported a strategic global partnership agreement that will enable the companies to offer BostonGene Tumor PortraitTM Tests in key international markets, including Japan as the first market outside of the U.S (Press release, NEC, DEC 14, 2021, View Source [SID1234597133]).

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BostonGene’s innovative computational platform performs AI-based molecular and immune profiling to discover correlations between tumor genomics, a patient’s immune system and the effectiveness of all available approved and experimental treatments. BostonGene Tumor Portrait Tests, based on integrated genomic and transcriptomic analysis, propel precision medicine into daily clinical practice and support physicians in actualizing personalized therapy for cancer patients.

Moreover, in NEC’s ongoing personalized neoantigen clinical trial that utilizes its AI-driven neoantigen prediction technology, NEC and BostonGene are collaborating to provide molecular characterization of patient tumors. Going forward, the two companies will jointly develop the market for BostonGene Tumor Portrait Tests globally. In Japan, the companies aim to utilize NEC’s healthcare and life science network in order to provide Tumor Portrait Tests to hospitals throughout the country.

In 2020, 378,385 people died of cancer in Japan, according to a Ministry of Health, Labor, and Welfare report. This accounts for 27.6% of all deaths that year and equates to one in four people dying of cancer. Leveraging NEC’s longstanding relationships with cancer centers, pharma and biotech companies, the organizations will work closely together to demonstrate the critical role of next generation multi-platform analytics combined with cutting-edge software to improve the diagnosis and treatment for cancer patients. Earlier this year, NEC announced an initiative to create healthcare and life science business that utilizes AI and other digital technologies as part of the "creation of future growth businesses" set forth in the 2025 Mid-term Management Plan.

"NEC has been committed to contributing to healthcare for more than half a century, which includes state-of-the-art hospital information systems in Japan. Cancer is now the country’s most common cause of death, and NEC has been working with the National Cancer Center Japan since 2016. Today, NEC remains as dedicated as ever to applying our rich experience in AI and analytics for improving patients’ outcomes," said Takayuki Morita, President and CEO at NEC Corporation. "BostonGene’s offering of deep molecular and immune profiling, coupled with its computational power and analytics, have already improved the quality of care for cancer patients in both academic and community settings in the United States. Supporting BostonGene’s international expansion enables us to continue to rapidly drive innovation that improves the standard of care in Japan and abroad."

"NEC has a long history of offering industry leading products and solutions in the field of healthcare both in Japan and globally," said Andrew Feinberg, President and CEO at BostonGene. "Partnering with NEC will allow BostonGene to expedite our international expansion which aims to improve the standard of care for cancer patients around the world."

This agreement expands upon existing collaborations between BostonGene and NEC.

On December 14, 2021 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported results from the Phase III POLARIX study showing that treatment with Polivy (polatuzumab vedotin) in combination with Rituxan (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) significantly reduced the risk of disease progression, relapse or death (progression-free survival; PFS) by 27% compared with the current standard-of-care, Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Safety outcomes were consistent with those seen in previous trials, and the safety profile was comparable for Polivy plus R-CHP versus R-CHOP (Press release, Genentech, DEC 14, 2021, View Source [SID1234597131]). Results were presented as a late-breaking abstract and during a press briefing at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition on Tuesday, December 14, 2021. Data from POLARIX were simultaneously published in the New England Journal of Medicine (NEJM).

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"As many as 40% of people with this aggressive lymphoma experience a return of their cancer after initial therapy, at which point they face a poor prognosis and limited treatment options," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "This Polivy-based regimen may conceivably change the disease course for many people with DLBCL, so we are working with health authorities around the world to make this important, potential new treatment option available as soon as possible."

"DLBCL is an aggressive disease and, despite continuous research efforts, there have been limited treatment advances in the frontline setting in the past 20 years," said Professor Hervé Tilly, POLARIX principal investigator and professor of hematology at the University of Rouen. "Results from the POLARIX trial represent an important advancement, bringing hope to people with this disease."

First efficacy and safety data from the pivotal Phase III POLARIX study showed a significant improvement in PFS with Polivy plus R-CHP versus R-CHOP in patients with previously untreated DLBCL after a median follow-up of 28.2 months (hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57–0.95; p<0.02). PFS is a clinically meaningful disease-related outcome for patients with previously untreated DLBCL as it represents the goals of first-line therapy: avoiding disease relapse, disease progression and death. The safety profile was comparable for Polivy plus R-CHP versus R-CHOP, including rates of Grade 3-4 adverse events (AEs; 57.7% versus 57.5%), serious AEs (34.0% versus 30.6%), Grade 5 AEs (3.0% versus 2.3%), and AEs leading to dose reduction (9.2% versus 13.0%). The POLARIX data form the basis of ongoing marketing applications to global health authorities.

Currently, Polivy is used as an off-the-shelf, fixed-duration treatment option in the relapsed or refractory (R/R) DLBCL setting and is approved in combination with bendamustine and Rituxan for the treatment of R/R DLBCL in more than 70 countries worldwide, including in the EU and in the United States. Genentech continues to explore areas of unmet need where Polivy has the potential to deliver benefit, with ongoing studies investigating combinations of Polivy with the CD20xCD3 T-cell engaging bispecific antibodies mosunetuzumab and glofitamab, with Venclexta (venetoclax), which is being developed by AbbVie and Genentech, and with Rituxan in combination with gemcitabine and oxaliplatin in the Phase III POLARGO study.

Follow Genentech on Twitter via @Genentech and keep up to date with ASH (Free ASH Whitepaper) 2021 news and updates by using the hashtag #ASH21.

About the POLARIX study
POLARIX [NCT03274492] is an international Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy (polatuzumab vedotin) plus Rituxan (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) versus Rituxan, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Eight-hundred and seventy-nine patients were randomized 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by Rituxan for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of Rituxan. The primary outcome measure is progression-free survival as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma. POLARIX is being conducted in collaboration with The Lymphoma Study Association (LYSA) and The Lymphoma Academic Research Organisation (LYSARC).

About Polivy (polatuzumab vedotin-piiq)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B cells, an immune cell impacted in some types of non-Hodgkin’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

Polivy U.S. Indication
Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat diffuse large B-cell lymphoma in adults who have progressed after at least two prior therapies.

The accelerated approval of Polivy is based on a type of response rate. There are ongoing studies to confirm the clinical benefit of Polivy.

Important Safety Information
Possible serious side effects
Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. A patient’s doctor may stop or adjust a patient’s treatment if any serious side effects occur. Patients must contact their healthcare team if there are any signs of these side effects.

Nerve problems in arms and legs: This may happen as early as after the first dose and may worsen with every dose. If a patient already has nerve pain, Polivy may make it worse. The patient’s doctor will monitor for signs and symptoms, such as changes in sense of touch, numbness or tingling in hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to walking patterns
Infusion-related reactions: A patient may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of the infusion
Infections: Patients should contact their healthcare team if they experience a fever of 100.4°F or higher, chills, cough, or pain during urination. Also, a patient’s doctor may give medication before giving Polivy, which may prevent some infections, and monitor blood counts throughout treatment with Polivy. Treatment with Polivy can cause severe low blood cell counts
Rare and serious brain infections: A patient’s doctor will monitor the patient closely for signs and symptoms of these types of infections. Patients should contact their doctor if they experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes
Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy
Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of the skin or the white part of the eyes. Patients may be at higher risk if they already have liver problems or are taking other medication
Side effects seen most often
The most common side effects during treatment were:

Low blood cell counts (platelets, red blood cells, white blood cells)
Nerve problems in arms and legs
Tiredness or lack of energy
Diarrhea
Nausea
Fever
Decreased appetite
Infections
Polivy may not be for everyone. A patient should talk to their doctor if they are:

Pregnant or may be pregnant: Data have shown that Polivy may harm an unborn baby
Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for at least 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for at least 5 months after their last Polivy treatment
Breastfeeding: Women should not breastfeed while taking Polivy and for at least 2 months after the last dose
These may not be all the side effects. Patients should talk to their healthcare provider for more information about the benefits and risks of Polivy treatment.