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 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, reported that it has completed its previously announced initial public offering (STAR Offering) on the Science and Technology Innovation Board (STAR Market) of the Shanghai Stock Exchange (SSE) (Press release, BeiGene, DEC 14, 2021, View Source [SID1234597276]). The shares offered in the STAR Offering were issued to and subscribed for by permitted investors in the People’s Republic of China (PRC) in Renminbi (RMB Shares). The RMB Shares began trading on the STAR Market under the stock code "688235" on December 15, 2021, China time, making BeiGene the first triple-listed biotechnology company on NASDAQ, the Hong Kong Stock Exchange (HKEx), and the STAR Market.

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The total number of shares offered in the STAR Offering is 115,055,260 ordinary shares, par value $0.0001 per share, which represents 8.62% of BeiGene’s total outstanding ordinary shares as of October 31, 2021, after giving effect to the shares offered. The public offering price of the RMB Shares is RMB192.60 per ordinary share, which equates to HK$234.89 per ordinary share and US$391.68 per American Depositary Share (ADS), based on an assumed exchange rate of RMB0.81996 to HK$1.00 and RMB6.3924 to US$1.00. Each ADS represents 13 ordinary shares.

The gross proceeds to BeiGene from the STAR Offering, before deducting underwriting commissions and other estimated offering expenses, are approximately RMB22.2 billion, or approximately US$3.5 billion, based on an assumed exchange rate of RMB6.3924 to US$1.00.

China International Capital Corporation Limited and Goldman Sachs Gao Hua Securities Company Limited acted as joint sponsors and joint bookrunners for the STAR Offering. J.P. Morgan Securities (China) Company Limited, CITIC Securities Co., Ltd. and Guotai Junan Securities Co., Ltd. acted as joint bookrunners for the STAR Offering.

BeiGene has granted China International Capital Corporation Limited a 30-day overallotment option for up to 17,258,000 additional RMB Shares. If the over-allotment option is fully exercised, the total number of shares offered in the STAR Offering will be 132,313,260 Shares, which represents 9.79% of BeiGene’s total outstanding ordinary shares as of October 31, 2021, after giving effect to the shares offered.

BeiGene expects to use the net proceeds from the STAR Offering to fund its research and clinical development, construction of its research and development centers and a manufacturing plant in China, sales and marketing force expansion in China, and for working capital and general corporate purposes.

In accordance with applicable PRC laws and regulations, the STAR Offering is conducted solely within the PRC and only to permitted investors who are eligible to participate in the STAR Offering in accordance with applicable PRC securities laws and regulations, and rules promulgated by the SSE and the China Securities Regulatory Commission (CSRC). The STAR Offering is conducted pursuant to a prospectus and other offering materials prepared by BeiGene in Chinese language and as approved by and registered with the SSE and the CSRC, which are only permitted to be used within the PRC. No part of the STAR Offering is intended to involve a public offering or sale of the RMB Shares into or in the United States or any other jurisdiction outside of the PRC. In addition, although the RMB Shares are of the same class and have the same rights as the Company’s existing ordinary shares listed on the HKEx, the RMB Shares will not be fungible with the ordinary shares listed on the HKEx or the Company’s ADSs representing its ordinary shares listed on the NASDAQ Global Select Market (NASDAQ), and in no event will any RMB Shares be able to be converted into ordinary shares listed on the HKEx or ADSs listed on NASDAQ, or vice versa.

An automatically effective shelf registration statement on Form S-3 was filed with the Securities and Exchange Commission (SEC) on May 11, 2020. A prospectus supplement relating to and describing the key terms of the STAR Offering was filed with the SEC and is available on the SEC’s website at www.sec.gov. The purpose of the prospectus supplement is to register all RMB Shares offered in the STAR Offering under the Securities Act of 1933, as amended (Securities Act) to ensure that the offer and sale of the RMB Shares, if any, to permitted investors who are U.S. persons (as defined in Regulation S under the Securities Act) in transactions outside the United States will not violate the registration requirements under Section 5 of the Securities Act.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any offer or sale of these securities in any state or 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 jurisdiction. This press release is being issued pursuant to, and in accordance with, Rule 134 under the Securities Act.

On December 14, 2021 PCI Biotech (OSE: PCIB), a clinical-stage biopharma company developing innovative therapeutics that address significant unmet medical needs in cancer reported that it has been invited to present at the DNB Nordic Healthcare Conference 2021, an Oslo based online event hosted by DNB (Press release, PCI Biotech, DEC 14, 2021, View Source [SID1234597416]).

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On Thursday, 16 December 2021 at 11:10 (CET), Dr. Per Walday, CEO, will present an overview of PCI Biotech’s proprietary platform technology via a general company presentation. The Company is also available for 1:1 meetings with potential partners and investors.

The presentation slides will be made available on PCI Biotech’s website (www.pcibiotech.com) under "Other presentations".

On December 14, 2021 Algok Bio Inc., a biopharmaceutical start-up based in Bellevue, Washington, developing next-generation therapeutics for unmet medical needs, reported a license agreement with Korea Atomic Energy Research Institute (KAERI) to obtain exclusive global rights of antibody technology targeting transmembrane 4 L six family member 4 (TM4SF4).

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TM4SF4 has been known to be a novel cell surface marker preferentially expressed in cancer stem cells and involved in the growth and metastasis of lung cancer. To inhibit the tumor-promoting effect of TM4SF4, KAERI successfully designed a mouse monoclonal antibody and manufactured a humanized antibody, maintaining its affinity but reducing immune rejection in the human body. KAERI also confirmed that it acts as a radio-sensitizer, preventing lung cancer cells from resistant to radiation therapy.

Algok Bio and KAERI will also have a research collaboration to support Algok Bio’s future development activities for 3 years, which are planned to be conducted in the US and South Korea.

(Press release, Algok Bio, DEC 14, 2021, View Source [SID1234662152])

On December 14, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported new analyses on the ongoing studies of HMPL-523 presented at the 63rd American Society for Hematology’s (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, held virtually and in person at the Georgia World Congress Center in Atlanta, Georgia (Press release, Hutchison China MediTech, DEC 14, 2021, View Source [SID1234597051]).

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Further details of the presentations are as follows:

Title: Safety, Pharmacokinetics, and Preliminary Efficacy of HMPL-523 in Adult Patients with Primary Immune Thrombocytopenia: A Randomized, Double-Blind and Placebo-Controlled Phase Ib Study
Presenter: Renchi Yang, MD, Hematology Hospital of the Chinese Academy of Medical Sciences
Session: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Treatment of Immune Thrombocytopenia
Abstract No.: 149895
Date & Time: Saturday, December 11, 2021 9:30am – 11am ET
Location: Georgia World Congress Center, C101 Auditorium and virtually

As of data cutoff date of September 30, 2021, a total of 34 patients were randomized to receive HMPL-523 and 11 patients to placebo. Among 16 patients who were randomized to receive the recommended phase II ("RP2D") dose of 300mg once daily, 11 patients (68.8%) experienced response as defined by at least one incident of platelet count being ≥ 50×109/L in the initial 8-week double blinded phase of the study, compared to one out of 11 patients (9.1%) randomized to receive placebo. During the subsequent 16-week open-label phase of the study, one additional patient initially randomized to receive the RP2D experienced a response. Four patients randomized to placebo crossed over to receive treatment at RP2D after the initial 8-week double blinded phase of the study; all four of these patients experienced response. In total, 16 out of 20 patients (80%) experienced response during both phases of the study. Durable response, defined as platelet count being ≥ 50×109/L in at least 4 out of 6 last scheduled visits, were reported in 8 out of 20 patients (40%) who received RP2D in both phases of the study.

Safety data were presented for all 41 patients who received treatment at all doses, regardless of whether they were initially randomized to receive active treatment or crossed over during the open-label extension phase of the study. The median duration of treatment was 142 days (range: 23-170). No patients discontinued treatment due to treatment-related adverse events ("TRAE"), and no cases of treatment-related serious adverse events ("SAE") were reported. There were 30 patients (73%) who experienced TRAEs, including 3 (7.3%) who experienced grade 3 or above TRAEs, one of whom received the RP2D. No TRAEs of grade 3 or above occurred in more than one patient.

These results supported the initiation of a Phase III registration study of HMPL-523 in adult patients with immune thrombocytopenia ("ITP"), ESLIM-01. The first patient in this study received their first dose on October 27, 2021. Additional details may be found at clinicaltrials.gov, using identifier NCT05029635.

Title: Preliminary Results from a Phase I Study of HMPL-523, a Selective, Oral Syk Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Paolo Strati, MD, The University of Texas MD Anderson Cancer Center
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemio­logical: Poster II
Abstract No.: 2432
Date & Time: Sunday, December 12, 2021 6:00pm – 8:00pm ET
Location: Georgia World Congress Center, Hall B5 and virtually

As of data cutoff date of August 25, 2021, 21 patients received a median of two cycles of treatment (range: 1-19). Among 16 response-evaluable patients, 4 responses were seen in patients in the 400-800 mg cohorts totaling 10 patients. Nine patients experienced disease progression, three in the 400-800mg cohorts and six in the 100-200mg cohorts.

Among 21 enrolled patients, 17 (81.0%) patients experienced TRAEs, including 7 (33.3%) who experienced grade 3 or above TRAEs. Specific to TRAE at grade 3 or above, neutropenia, which occurred in 2 patients, was the only TRAEs of grade 3 or above to have occurred in more than one patient. SAEs were reported in 6 patients (28.6%). Adverse events leading to discontinuation were reported in 2 (9.5%) patients. 7 patients withdrew from the study for reasons other than progressive disease.

These results support progressing HMPL-523 into the ongoing dose expansion phase of the study to evaluate its safety and efficacy in multiple subtypes of B-cell and T-cell lymphoma at the R2PD of 700 mg.

About HMPL-523
HMPL-523 is a novel, investigational, selective small molecule inhibitor for oral administration targeting spleen tyrosine kinase, also known as Syk. Syk is a major component in B-cell receptor signaling and is an established target for the treatment of multiple subtypes of B-cell lymphomas and autoimmune disorders.

HUTCHMED currently retains all rights to HMPL-523 worldwide. The ESLIM-01 Phase III trial is underway to evaluate the efficacy and safety of HMPL-523 in treating adult patients with primary ITP, an autoimmune disorder that can lead to increased risk of bleeding. Additional details may be found at clinicaltrials.gov, using identifier NCT05029635. HMPL-523 is also being studied in indolent non-Hodgkin’s lymphoma and multiple subtypes of B-cell malignancies in China (NCT02857998), the U.S. and Europe (NCT03779113). A trial to study HMPL-523 in patients with warm autoimmune hemolytic anemia (wAIHA), another autoimmune disorder, is also planned.