On December 9, 2024 Protara Therapeutics, Inc. (Nasdaq: TARA) ("Protara"), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported the pricing of its underwritten public offering of 13,690,000 shares of its common stock at a price to the public of $6.25 per share and pre-funded warrants to purchase 2,325,372 shares of common stock at a price of $6.249 per pre-funded warrant, which represents the per share price for the common stock less the $0.001 per share exercise price for each such pre-funded warrant (Press release, Protara Therapeutics, DEC 10, 2024, View Source [SID1234648992]). In addition, Protara has granted the underwriters a 30-day option to purchase up to an additional 2,402,305 shares of common stock at the public offering price, less underwriting discounts and commissions. All shares and pre-funded warrants in the offering are being sold by Protara. The gross proceeds from the offering are expected to be approximately $100 million before deducting underwriting discounts and commissions and offering expenses payable by Protara and excluding any exercise of the underwriters’ option to purchase additional shares and the exercise of any pre-funded warrants. The offering is expected to close on December 11, 2024, subject to satisfaction of customary closing conditions. Protara intends to use the net proceeds received from the offering to fund the clinical development of TARA-002, as well as the development of other clinical programs. Protara may also use the net proceeds from the offering for working capital and other general corporate purposes.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

TD Cowen, Cantor, LifeSci Capital, Oppenheimer & Co. and Scotiabank are acting as joint book-running managers of the offering.

The shares of common stock and the pre-funded warrants will be issued pursuant to an effective shelf registration statement on Form S-3 (File No. 333-275290) that was declared effective on November 14, 2023 by the U.S. Securities and Exchange Commission (the "SEC"). The offering is being made only by means of a prospectus supplement and the accompanying prospectus. A final prospectus supplement relating to the offering will be filed with the SEC and will be available on the SEC’s website, located at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering, when available, may be obtained from the offices of TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, New York 10017, by email at [email protected] or by telephone at (855) 495-9846; Cantor Fitzgerald & Co., 110 East 59th Street, 6th Floor, New York, New York 10022, Attention: Capital Markets, or by email at [email protected]; or LifeSci Capital LLC, 1700 Broadway, 40th Floor, New York, New York 10019, or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the applicable securities laws of such state or jurisdiction.

On December 10, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing, and commercializing therapies to address global unmet medical needs primarily for malignancies, reported that it has released the latest clinical data of lisaftoclax (APG-2575) as a monotherapy or in combinations in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), in a Poster Presentation at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in San Diego, CA, the United States (Press release, Ascentage Pharma, DEC 10, 2024, View Source;ascentage-pharmas-bcl-2-inhibitor-lisaftoclax-in-combinations-demonstrates-potential-clinical-benefit-in-patients-with-prior-exposure-to-venetoclax-302327542.html [SID1234649008]). Dr. Matthew Davids, from Dana-Farber Cancer Institute in the US, is the principal investigator of the study.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The ASH (Free ASH Whitepaper) Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, results from multiple clinical and preclinical studies on four of Ascentage Pharma’s drug candidates (olverembatinib, lisaftoclax, APG-2449, and APG-5918) have been selected for presentations, including two Oral Reports, at this year’s ASH (Free ASH Whitepaper) Annual Meeting.

These data once again highlighted the therapeutic magnitude of Ascentage Pharma’s Bcl-2 selective inhibitor lisaftoclax, as a monotherapy and in combinations, in patients with relapsed/refractory (R/R) CLL/SLL, particularly the clinical benefit of lisaftoclax in combination with acalabrutinib in patients with prior exposure to venetoclax, including those who progressed on or were intolerant/refractory to venetoclax. Furthermore, no drug-drug interactions (DDIs) or new safety signals were observed in patients treated with lisaftoclax monotherapy or combinations.

Dr. Matthew S. Davids commented, "Lisaftoclax continues to demonstrate very strong efficacy in multiple patient subgroups, including those who previously progressed on venetoclax or BTK inhibitors. The drug also has excellent tolerability and the convenience of a daily dose ramp-up to reach the target effective dose. Based on the promising early phase results, the GLORA global registrational study has now launched and is actively enrolling."

"Results released at this year’s ASH (Free ASH Whitepaper) Annual Meeting reaffirmed the therapeutic potential of lisaftoclax in CLL/SLL," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "In China, a New Drug Application (NDA) for lisaftoclax has already been accepted and granted the Priority Review designation by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA), potentially leading lisaftoclax to become the second Bcl-2 inhibitor approved anywhere in the world. In the US, a global registrational Phase III study that was cleared by the US Food and Drug Administration (FDA) is currently underway. Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will expedite the global clinical development of our key drug candidates such as lisaftoclax to bring more safe and effective therapies to patients as soon as possible."

Highlights of the data this study reported at ASH (Free ASH Whitepaper) 2024 are as below:

Lisaftoclax (APG-2575) Demonstrates Activity and Safety When Given With Accelerated Ramp-up and Then Combined With Acalabrutinib or Rituximab in Patients (pts) With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Including Those With Prior Exposure to Venetoclax
Format: Poster Presentation
Abstract#: 4614
Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III

Highlights:

Background: Bcl-2 inhibition with venetoclax (ven) was a major advance in CLL treatment, but the 5-week dose ramp-up to mitigate the risk of tumor lysis syndrome (TLS) and DDIs challenge treatment optimization. Lisaftoclax is an investigational, oral Bcl-2i with a short half-life, allowing it to be ramped-up on a daily schedule.

Introduction: This poster presents updated clinical data of lisaftoclax alone or combined with acalabrutinib or rituximab in patients with treatment-naïve (TN), R/R, or prior ven-treated CLL/SLL.

Enrolled Patients and Study Methods:

From March 20, 2020, to June 27, 2024, 176 patients were enrolled: 46 in monotherapy and 39 and 91 in the rituximab and acalabrutinib combination cohorts, respectively; 87.5% (154/176) of patients were R/R and 12.5% (22/176) were TN. The median (range) age was 63 (34-80) years; 67% were male; 25.6% had del(17p) and/or TP53 mutation.
Median (range) duration of treatment with lisaftoclax was 16.5 (1-54; monotherapy), 24 (3-39; rituximab), and 27 (1-43; acalabrutinib) cycles. Fourteen (9%) patients relapsed on or were intolerant /refractory to prior treatment with ven. Their median (range) age was 65 (51-78) and 79% were male. 50% of those patients had del (17p), 36% had the TP53 mutation, 64% had del (11q), 38% had a complex karyotype (≥ 3 abnormalities), and 92% had unmutated IGHV.
Patients were treated with a rapid 4- to 6-day daily ramp-up of lisaftoclax from 20 mg to a target dose of 400, 600, or 800 mg, receiving daily oral lisaftoclax alone or, plus continuous acalabrutinib or 6 cycles of rituximab in 28-day cycles, starting on Cycle 1 Day 8 (C1D8) until disease progression, complete response by C24, or unacceptable toxicity.
Efficacy Results:

The ORR for lisaftoclax plus acalabrutinib in 87 patients was 98%, and the median duration of response (DOR; 95% CI, 31-NE) and median progression-free survival (PFS; 95% CI, 34-NE) of responders were not reached.

Among patients who received lisaftoclax plus acalabrutinib, 14 have relapsed on or were intolerant/refractory to prior treatment with ven. Their median (range) cycles of treatment were 16 (3-25), the ORR was 86%, the median PFS was not reached (11.3-NE), the 12-month PFS rate was 84%, and the 18-month PFS rate was 73%.
Among patients who received lisaftoclax plus acalabrutinib, 9 were refractory to ven. Their median (range) cycles of treatment were 16 (3-25), the ORR was 89%. The median PFS was not reached (NE-NE), the 12-month PFS rate was 89%, and the 18-month PFS rate was 89%.
Safety Results:

Incidence and severity of TEAEs were similar across cohorts.
Common (≥20%) any-grade TEAEs in all cohorts combined were infection (107 [61%]), neutropenia (67 [38%]), anemia (51 [29%]), diarrhea (51 [29%]), and thrombocytopenia (38 [22%]). Grade ≥ 3 treatment-emergent AEs (TEAEs；≥10%) were neutropenia in 15 (33%), 11 (28%), and 27 (30%) patients; infection in 13 (28%), 4 (10%), and 14 (15%) patients; and anemia in 8 (17%), 4 (10%), and 11 (12%) patients in monotherapy, rituximab, and acalabrutinib combination cohorts, respectively.
Lisaftoclax, alone or in combination, demonstrated a favorable safety profile and a rate of clinical tumor lysis syndrome (TLS) of 1.1%. No DDIs or new safety signals were observed in patients who received lisaftoclax in combination with acalabrutinib or rituximab.
Conclusions: The presented data suggest that lisaftoclax combined with acalabrutinib was active in patients with TN or R/R CLL, with a reported 98% ORR and a median DOR that was not reached at 22.3 months of median follow-up. Lisaftoclax combined with acalabrutinib was also effective for patients with prior ven exposure, including those who progressed on or were intolerant/refractory to ven. In this updated analysis with longer follow-up, no DDIs or new safety findings were observed in TN or R/R CLL/SLL patients treated with lisaftoclax monotherapy or combinations. Patients with prior ven exposure continue to be accrued in order to further evaluate this promising signal. A global registrational phase III study is recruiting.

*Lisaftoclax is an investigational drug that has not been approved in any country and region.

On December 9, 2024 Cimeio Therapeutics reported that it has entered a research collaboration with Kyowa Kirin Co., Ltd. (Kyowa Kirin) to develop a novel therapy for diseases with high unmet need (Press release, Cimeio Therapeutics, DEC 10, 2024, View Source [SID1234648894]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The partnership combines Cimeio’s proprietary Shielded Cell and Immunotherapy (SCIP) platform with Kyowa Kirin’s expertise in cellular therapies and underscores both companies’ commitment to using emerging cell and gene therapy technologies to develop new ways to treat patients. Under the terms of the agreement, Cimeio is eligible to receive an upfront payment and two years of research funding. Upon Kyowa Kirin’s exercise of a commercial license option, Cimeio will be eligible for development and commercial milestones as well as royalties on sales of potential products arising from the partnership. Further terms are not disclosed.

Cimeio’s SCIP platform is based on the development of novel immunotherapies enabled by epitope-shielded cells. These cells contain modified variants of naturally occurring cell surface proteins that maintain their function but are resistant to depletion by the paired immunotherapy. These shielded cells enable the development of powerful therapeutics for previously undruggable targets, targeted conditioning for HSC transplant, and immune system reset amongst other applications.

"We are thrilled to collaborate with Kyowa Kirin, a company with a rich history of investing in innovative technologies that have the potential to significantly improve outcomes for patients with serious conditions," said Dr. Stefanie Urlinger CSO of Cimeio. "This partnership represents a significant step forward for our company and mission."

"Kyowa Kirin and Cimeio share the vision for the potential of therapeutics enabled by epitope-shielded cells," said Yoshifumi Torii, Ph.D, Executive Officer, Senior Vice President, Head of Research Division of Kyowa Kirin. "With this partnership we believe we can develop a safe and effective therapy for diseases that in the past have been incredibly difficult to treat, and we’re looking forward to working with the talented team at Cimeio."

On December 10, 2024 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that new and updated data from its industry-leading CD20xCD3 T-cell-engaging bispecific antibody programme were presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, 7-10 December 2024 (Press release, Hoffmann-La Roche, DEC 10, 2024, View Source [SID1234648977]). With more than 20 bispecific antibody abstracts accepted for presentation, data showcase the benefits of fixed-duration Columvi (glofitamab) and Lunsumio (mosunetuzumab) across different types of aggressive and indolent lymphomas. This research supports Roche’s efforts to continue innovating for patients by advancing treatment standards at earlier stages of disease while exploring additional forms of administration that could further improve the patient experience.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The data being presented at ASH (Free ASH Whitepaper) offer further evidence that Columvi and Lunsumio can provide lasting remissions for people with advanced lymphoma," said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. "The results underscore our ambition to transform the treatment of B-cell malignancies with a range of innovative therapeutic options."

"Lymphoma patients face challenges that extend well beyond the clinical manifestations of their disease, including the physical and emotional strain of frequent appointments and treatments," said Elizabeth Budde, M.D., Ph.D., City of Hope’s executive medical director of its Enterprise Immune Effector Cell Program and associate professor in its Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation. "While Lunsumio’s fixed duration intravenous formulation has already offered a valuable treatment option, the introduction of a subcutaneous route could provide a shorter administration time. With both routes available, we can better tailor therapy to each patient’s needs, supporting a flexible and patient-centered approach to follicular lymphoma care."

Follow-up data reinforce benefits of fixed-duration therapies beyond the end of treatment
Three-year follow-up from the pivotal phase II NP30179 study of Columvi in people with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) showed 40.0% of patients achieved a complete response (CR), with a median duration of CR of 29.8 months (95% CI: 22.0–not estimable [NE]). The majority of patients in complete remission at the end of therapy remained in remission two years after therapy completion. Safety appeared consistent with the previous analysis.1

Long-term data at four years from the pivotal phase II GO29781 study of Lunsumio in patients with R/R follicular lymphoma (FL) showed long-lasting remissions, with nearly two-thirds (64.0% [95% CI: 50.1-78.0]) of patients with a CR alive and without disease progression at 45 months. The overall response rate (ORR) and CR rates in the overall population were 77.8% and 60.0%, respectively. Consistent results were seen in patients with a history of disease progression within 24 months of frontline treatment (POD24), which is typically harder to treat. No new safety signals were observed since the previous analysis.2

Both studies also showed restoration of B-cell levels, starting from 12-18 months following Columvi treatment and after a median of 19 months following Lunsumio treatment, indicating immune system recovery and supporting the use of a fixed-duration treatment approach.1,2 Recovery of B cells following treatment for lymphoma is important so that patients can maintain immune system function.

A US real-world data study and economic model evaluating R/R non-Hodgkin lymphoma patient treatment-related travel burden across different bispecific antibody therapies highlight the impact of travel distance, time and associated costs, an often-overlooked aspect of the patient experience beyond clinical efficacy and safety. These factors play a crucial role in treatment decision-making, further emphasising the importance of patient-centred treatment options. The study found fixed-duration therapies, such as Columvi and Lunsumio, reduce treatment-related travel burden due to less frequent dosing.3

Studies investigating subcutaneously-administered Lunsumio show positive results
Data from a primary analysis of the phase II GO29781 study of investigational Lunsumio administered subcutaneously in patients with third-line or later FL were presented for the first time. Results show pharmacokinetic non-inferiority compared to intravenous (IV) administration, with fixed-duration Lunsumio achieving high rates of deep and durable remissions, with 76.6% of patients experiencing an ORR and a 61.7% CR rate, as evaluated by the independent review committee. The median progression-free survival was 23.7 months (95% CI: 14.6-NE), while the median overall survival was not reached. The most common all-grade adverse events (AEs) were injection-site reactions (60.6%; all Grade 1-2), fatigue (35.1%), and cytokine release syndrome (CRS; 29.8%). The rate and severity of CRS events were low (Grade 1-2, 27.6%; Grade 3, 2.1%); all occurred during cycle 1 and were resolved.4 Data has been submitted to health authorities with the aim of offering patients and healthcare providers an alternative treatment and more choice when it comes to administration options depending on their needs.

New data from a randomised phase II cohort of the investigational GO40516 study showed improved efficacy and manageable safety with outpatient, subcutaneously administered, fixed-duration Lunsumio in combination with Polivy (polatuzumab vedotin) versus MabThera/Rituxan (rituximab) in combination with Polivy, in people with R/R LBCL. In the Lunsumio-Polivy arm, the ORR was 77.5% (95% CI: 61.6-89.2) versus 50.0% (95% CI: 33.8–66.2) for MabThera/Rituxan-Polivy, and the CR rate was 57.5% (95% CI: 40.9-73.0) versus 35.0% (95% CI: 20.6-51.7). AEs of special interest occurring in ≥30% of patients in the Lunsumio-Polivy arm were injection-site reactions (55.0%) and neutropoenia (40.0%). CRS events occurred in four (10.0%) patients, all of which were Grade 1-2, occurred during cycle 1 and were resolved.5 These data support further exploration of this investigational treatment combination in the ongoing phase III SUNMO study, which could provide an alternative option in second-line DLBCL to meet diverse patient needs.

Additional data support Roche’s goal to elevate treatment standards in earlier stages of LBCL
Updated data from the phase I/Ib investigational NP39488 study showed high and durable response rates in people with R/R LBCL treated with Columvi in combination with Polivy, including those with high-grade disease and prior treatment with CAR T-cell therapy. Of the 128 efficacy-evaluable patients, the best ORR was 80.6%, with a CR rate of 62.0%, and the median duration of CR was 31.8 months (95% CI: 21.9-NE). Among patients previously treated with CAR T-cell therapy (n=28), the ORR was 75.0%, with a CR rate of 50.0%. The safety profile was manageable and consistent with the known profiles of the individual drugs. The most common AE was CRS (44.4%), which was mostly Grade 1-2.6 Results support ongoing development of this investigational combination in the phase III SKYGLO study investigating Columvi with Polivy-MabThera/Rituxan, cyclophosphamide, doxorubicin and prednisone (R-CHP) in previously untreated DLBCL.

About Columvi (glofitamab)
Columvi is a CD20xCD3 T-cell-engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Columvi was designed with a novel 2:1 structural format. This T-cell-engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. Roche is investigating Columvi as a monotherapy and in combination with other medicines for the treatment of diffuse large B-cell lymphoma and mantle cell lymphoma.

About Lunsumio (mosunetuzumab)
Lunsumio is a first-in-class CD20xCD3 T-cell-engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. This dual-targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development programme for Lunsumio is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, and other blood cancers.

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

On December 10, 2024 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that the pre-specified threshold of 60 events (deaths) has been reached in its ongoing Phase 3 REGAL clinical trial of galinpepimut-S (GPS) in acute myeloid leukemia (AML), triggering the interim analysis to be conducted by the Independent Data Monitoring Committee (IDMC) (Press release, Sellas Life Sciences, DEC 10, 2024, View Source [SID1234648993]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The IDMC will conduct a thorough review of the current REGAL data, and the interim analysis will provide an assessment of efficacy, futility as well as safety of GPS.

"This is an exciting and very important milestone in our efforts to bring forward a new potential treatment option for AML patients," said Angelos Stergiou, MD, ScD hc, President and Chief Executive Officer of SELLAS. "Our mission at SELLAS is to develop novel therapies that prolong patients’ lives, and the outcome of the interim analysis will hopefully bring us closer to the potential of adding GPS as a powerful ally in the battle against AML. Today, we are here thanks to the unwavering support of our shareholders, dedication of our clinical investigators and the resilience of our patients and their families. The IDMC will now carefully review and analyze all the data and have scheduled a meeting in January to review results to date. We are extremely grateful to everybody who have contributed to the REGAL study, and we look forward to sharing the IDMC’s feedback and recommendations as soon as they become available."

The Company will host a call today to review the process leading up to the IDMC meeting and the potential outcomes of the REGAL interim analysis.

To access the webinar, please use the following information:

Date: Tuesday, December 10, 2024
Time: 9:00 a.m. Eastern Time
Webcast: SELLAS GPS REGAL