On March 14, 2024 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company developing investigational first-in-class telomerase inhibitor, imetelstat, to treat hematologic malignancies, reported that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 12 to 2 in favor of the clinical benefit/risk profile of imetelstat for the treatment of transfusion-dependent (TD) anemia in adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs) (Press release, Geron, MAR 14, 2024, View Source [SID1234641163]).

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!

"We are pleased with the Committee’s decision to recognize the positive clinical benefit/risk profile of imetelstat for the treatment of transfusion-dependent anemia in adult patients with lower-risk MDS. There are few treatment options and significant unmet medical need remains for these patients, particularly among those with difficult-to-treat subtypes of this blood cancer," said Faye Feller, M.D., Geron’s Executive Vice President, Chief Medical Officer. "We believe that imetelstat has the potential to be an important new medicine for patients and look forward to continuing our collaboration with the FDA as they complete their review of our New Drug Application."

The ODAC reviewed the results from the IMerge Phase 3 clinical trial. The primary endpoint of red blood cell transfusion independence (RBC-TI) for at least eight consecutive weeks was significantly higher with imetelstat vs. placebo (p<0.001), with median RBC-TI duration approaching one year for imetelstat ≥8-week RBC-TI responders. In addition, 28% of imetelstat-treated patients compared to 3% on placebo obtained a statistically significant improvement in the key secondary endpoint of at least 24-week RBC-TI. For those patients achieving ≥24-week RBC-TI, the median duration was 80 weeks. Clinically meaningful RBC-TI was achieved across key MDS subgroups irrespective of ring sideroblast (RS) status, baseline transfusion burden and International Prognostic Scoring (IPSS) risk category. Additionally, a sustained increase in mean hemoglobin levels in imetelstat-treated patients was observed over time compared to placebo patients. Consistent with prior imetelstat clinical experience, the most common Grade 3-4 adverse events were thrombocytopenia (62%) and neutropenia (68%) that were generally manageable and of short duration.

The FDA assigned a Prescription Drug User Fee Act (PDUFA) target action date of June 16, 2024 for Geron’s New Drug Application (NDA) for imetelstat for the treatment of TD anemia in adult patients with low- to intermediate-1 risk myelodysplastic syndromes, who have failed to respond, or have lost response to, or are ineligible for ESAs. The ODAC provides the FDA with independent opinions and recommendations from outside medical experts, patients and caregivers, though the recommendations are not binding. Geron plans to commercially launch imetelstat in the U.S. upon potential FDA approval.

About IMerge Phase 3

The Phase 3 portion of the IMerge Phase 2/3 trial is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower-risk) transfusion-dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a hypomethylating agent or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion-dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of red blood cell transfusion independence (RBC-TI) lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week RBC-TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week RBC-TI), the duration of RBC-TI and the rate of hematologic improvement erythroid (HI-E), which is defined under 2006 IWG criteria as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, the Middle East and Asia.

About Imetelstat

Imetelstat is a novel, first-in-class investigational telomerase inhibitor exclusively owned by Geron and being developed by Geron in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat 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. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion-dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk myelofibrosis (MF) whose disease has relapsed after or is refractory to Janus kinase (JAK) inhibitor treatment. Imetelstat is currently not approved by any regulatory authority.

On March 14, 2024 Tubulis reported the successful completion of an upsized and oversubscribed €128 million ($138.8 million) Series B2 financing (Press release, Tubulis, MAR 14, 2024, View Source [SID1234641162]). The round was co-led by EQT Life Sciences and Nextech Invest Ltd, on behalf of one or more funds managed by it, with participation from new US-based funds, Frazier Life Sciences and Deep Track Capital as well as all existing investors, including Andera Partners, BioMedPartners, Fund+, Bayern Kapital (with ScaleUp-Fonds Bayern), Evotec, coparion, Seventure Partners, OCCIDENT and High-Tech Gründerfonds (HTGF). Tubulis is developing a pipeline of uniquely matched antibody drug conjugates (ADCs) with an indication-tailored targeting molecule and payload combination to develop novel ADCs with superior properties.

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 proceeds of the Series B2 will primarily support progress in Tubulis’ pipeline of next-generation ADCs toward clinical evaluation and help achieve clinical proof-of-concept for lead candidates, TUB-040 and TUB-030. TUB-040 addresses tumor-antigen Napi2b, a well-characterized target in ovarian and lung cancer and TUB-030 targets 5T4, an antigen often overexpressed in solid tumors. Preclinical proof-of-concept data for these two candidates will be presented at the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in April. The company expects to start its first Phase 1/2a clinical trial, including dose escalation and dose optimization cohorts in 2024. The capital will also fund the expansion of Tubulis’ suite of technology platforms to unlock novel payloads for the development of versatile and customizable ADCs. In line with the addition of new US investors, Tubulis plans to increase its corporate footprint by establishing a US subsidiary.

"This substantial financing from a syndicate of global specialist biotech investors recognizes Tubulis’ unique position in the ADC space. Our proprietary platform technologies and internal know-how are the foundation for our pipeline of truly differentiated protein-drug conjugates," said Dominik Schumacher, PhD, CEO and Co-founder of Tubulis. "Our goal is to establish Tubulis as a global ADC leader as we transition into a clinical-stage company and harness the full power of ADCs to bring their therapeutic value to patients with solid tumors."

In conjunction with the financing, Christoph Broja, Managing Director at EQT Life Sciences and Kanishka Pothula, Managing Partner at Nextech Invest will join Tubulis’ Supervisory Board. An overview of all members as well as their biographies can be found here.

Kanishka Pothula, Managing Partner at Nextech Invest commented: "Recent developments in oncology underscore the significant potential of ADCs for the treatment of solid tumors. We are convinced that Tubulis will be at the forefront of this next wave of ADC therapeutics. The team continuously pushes the boundaries of ADC design and has developed an impressive set of platform technologies that give the company the full flexibility to tailor each component of the ADC to a specific indication. The company is on the path towards providing new, high-quality treatment options for many hard-to-treat cancers and we are excited to join their journey by providing strategic support in the next phase of corporate growth."

"Dominik and the Tubulis team have developed highly differentiated ADC candidates that have the potential to significantly change the treatment paradigm in targeted solid tumor indications. We are looking forward to supporting the Tubulis team in realizing their vision of delivering the true value of ADCs by extending patient benefit and improving quality of life, said Christoph Broja, Managing Director at EQT Life Sciences. At EQT, we are focused on guiding the next global leaders in healthcare and Tubulis is well positioned to directly impact the future of oncology treatments," added John de Koning, Partner at EQT Life Sciences.

Tubulis was established with the goal of maximizing the overall performance of ADCs by addressing the main bottlenecks in the field through innovation in all aspects of ADC development. The company has created a unique suite of technologies that combine a diverse range of targeting molecules, innovative payloads, and proprietary conjugation technologies to deliver revolutionary ADCs with superior, indication-tailored properties. The company’s platforms allow it to move beyond traditional payload classes and expand antibody conjugation options through novel chemical groups, resulting in stable, high drug-to-antibody ratios.

¹Nextech Invest Ltd, on behalf of one or more funds managed by it.

On March 14, 2024 Cullinan Oncology, Inc. (Nasdaq: CGEM; "Cullinan"), a biopharmaceutical company focused on developing modality-agnostic targeted oncology therapies, reported on recent and upcoming business highlights and announced its financial results for the fourth quarter and full year ended December 31, 2023 (Press release, Cullinan Oncology, MAR 14, 2024, View Source [SID1234641161]). The company also announced that Chief Financial Officer Jeff Trigilio will depart the company effective March 29. Following his departure, Jeff has agreed to support the company through a transition period.

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!

"With the remarkable progress we made in 2023, we are positioned for an exciting, data-rich 2024," said Nadim Ahmed, Chief Executive Officer of Cullinan Oncology, "We are on track to present clinical data across multiple programs, starting first with our lead unpartnered program, CLN-619. We plan to present initial data assessing CLN-619 in combination with checkpoint inhibitor therapy, along with updated data from the monotherapy dose escalation module, at a major medical meeting in the second quarter. We are exploring development of CLN-978, our next generation CD19xCD3 T cell engager, for the treatment of autoimmune diseases, where we believe it has significant potential as a potent, off-the-shelf, patient-friendly alternative to CAR T cell therapy. We continue to advance a broad zipalertinib development program in collaboration with Taiho, and we are on track to complete enrollment in the pivotal Phase 2b portion of the REZILIENT1 study by the end of the year. Lastly, we thank Jeff Trigilio for playing an important role in transitioning the company from an early-stage private biotechnology company to a public company with a diversified and deep pipeline and we wish him the best in his future endeavors."

Portfolio Highlights

•
CLN-619 (Anti-MICA/MICB monoclonal antibody): Solid tumors and hematological malignancies
o
Enrollment continues in the ongoing Phase 1 study evaluating CLN-619 as both monotherapy and in combination with checkpoint inhibitor therapy for patients with advanced solid tumors. Accrual to the dose escalation phase of
the combination module has been completed. Recruitment continues in the monotherapy disease specific expansion cohorts for patients with endometrial and cervical cancers. Cullinan also continues to evaluate potential additional disease specific expansion cohorts.
o
Cullinan remains on track to report initial data from the combination dose escalation module as well as an update on the monotherapy dose escalation module at a medical conference in the second quarter of 2024.
o
Cullinan also remains on track to report initial data from disease specific dose expansion cohorts in the first half of 2025.
o
Cullinan recently received FDA clearance for an IND for CLN-619 in multiple myeloma.
•
CLN-978 (CD19xCD3 T cell engager): B-NHL, autoimmune disorders
o
In August 2023, Cullinan dosed the first patient in our Phase 1 clinical trial of CLN-978 in patients with relapsed/refractory B cell non-Hodgkin lymphoma. Based on emerging clinical data and case series from academic and industry groups supporting the efficacy of CD19 directed CAR T cell therapy in multiple autoimmune diseases and our belief that CLN-978 may address the limitations of CAR T cell therapy, Cullinan is exploring development of CLN-978 in autoimmune diseases.
o
CLN-978 incorporates several design features to address the limitations of other approaches, specifically: 1) an albumin binding, half-life extending domain that allows for weekly dosing; 2) high-affinity binding to CD19, enabling elimination of B cells with very low CD19 expression; and 3) subcutaneous administration, which can potentially reduce cytokine release and allow for better tolerability and convenience.
o
Cullinan’s non-human primate data show that subcutaneous administration of CLN-978 achieved profound B cell depletion in the periphery and in tissues such as lymph nodes and spleen. Moreover, subcutaneous administration of CLN-978 in non-human primates was better tolerated and led to markedly decreased cytokine induction compared to intravenous administration. Finally, in vitro studies showed CLN-978 could eliminate B cells expressing extremely low levels of CD19.
•
Zipalertinib (EGFR ex20ins inhibitor), collaboration with Taiho Oncology: EGFR ex20ins NSCLC
o
Cullinan expects to complete enrollment in the pivotal Phase 2b portion of the REZILIENT1 study in patients with EGFR ex20ins NSCLC who have progressed after prior systemic therapy, with or without exon 20 targeted therapy, by year-end 2024.
•
CLN-049 (FLT3xCD3 T cell-engaging bispecific antibody): AML and MDS
o
Cullinan expects to provide a clinical data update from the ongoing Phase 1 multi-ascending dose study in r/r AML and MDS patients in the second half of 2024.

•
CLN-418 (B7H4x4-1BB bispecific immune activator): Solid tumors
o
Cullinan expects to provide a clinical data update from the ongoing Phase 1 dose escalation study in patients with advanced solid tumors in the second half of 2024.
•
CLN-617 (IL-2 and IL-12 cytokine fusion protein): Solid tumors
o
Enrollment continues in the ongoing Phase 1 study in patients with advanced solid tumors.
Fourth Quarter 2023 Financial Results

•
Cash Position: Cash, cash equivalents, investments, and interest receivable were $468.3 million as of December 31, 2023. Cullinan expects its cash resources to provide runway into the second half of 2026 based on its current operating plan.
•
R&D Expenses: Research and development (R&D) expenses were $34.8 million for the fourth quarter of 2023, compared to $33.8 million for the third quarter of 2023. R&D expenses for the fourth and third quarters of 2023 included $2.7 million and $3.2 million of equity-based compensation expenses, respectively. The increase in R&D expenses was primarily related to increases in clinical costs, partially offset by decreases in CMC costs.
•
G&A Expenses: General and administrative (G&A) expenses were $10.6 million for the fourth quarter of 2023, compared to $11.0 million for the third quarter of 2023. G&A expenses in the fourth and third quarters of 2023 included $4.9 million and $4.5 million of equity-based compensation expenses, respectively. The decrease in G&A expenses was primarily driven by decreases in legal and professional fees.
•
Net Loss: Net loss (before items attributable to noncontrolling interest) for the fourth quarter of 2023 was $25.6 million, compared with net loss of $39.2 million for the third quarter of 2023. Net losses included the items described above, partially offset by interest income of $5.9 million in each of the fourth and third quarter of 2023 and a $14.1 million income tax benefit related to a 2022 return-to-provision adjustment and 2023 federal R&D tax credits that can be carried back to 2022 that were recorded in the fourth quarter of 2023.
Full Year 2023 Financial Results

•
R&D Expenses: R&D expenses were $148.2 million for 2023, compared to $91.9 million for 2022. R&D expenses for 2023 and 2022 included $12.2 million and $11.0 million of equity-based compensation expenses, respectively. The increase in R&D expenses for 2023 compared to 2022 was primarily due to a one-time upfront payment related to in-licensing CLN-418 in 2023, higher personnel costs due to increased headcount and expansion of operations to support our research and development activities, and higher equity-compensation costs, partially offset by decreased of lower preclinical costs.
•
G&A Expenses: G&A expenses were $42.5 million for 2023, compared to $40.2 million for 2022. G&A expenses for 2023 and 2022 included $18.3 million and $16.9 million of equity-based compensation expenses, respectively. The increase in G&A expenses was primarily due to an increase in personnel costs, higher equity-based compensation costs, and higher occupancy and other costs to support our expanded operations, partially offset by one-time costs related to the sale of Cullinan Pearl in 2022 that did not recur in 2023, and lower legal and other professional service fees.
•
Net Loss: Net loss (before items attributable to noncontrolling interest) for 2023 was $155.1 million, compared with net income of $109.2 million for 2022. Net losses in 2023 and net income in 2022 included the items described above, partially offset by interest income of $21.6 million and $6.6 million for 2023 and 2022, respectively, and a $14.1 million income tax benefit related to a 2022 return-to-provision adjustment and 2023 federal R&D tax credits that can be carried back to 2022 that were recorded in 2023.
•
Shares Outstanding: As of March 1, 2024, Cullinan had 43,065,645 shares of common stock outstanding plus 647,500 shares of non-voting preferred stock outstanding, each of which is convertible into 10 shares of common stock.

On March 14, 2024 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it filed regulatory applications with the Ministry of Health, Labour and Welfare for the anti-CD20xCD3 bispecific antibody mosunetuzumab for the treatment of patients with R/R FL who have received two or more prior systemic therapies (Press release, Chugai, MAR 14, 2024, View Source [SID1234641159]).

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!

"Mosunetuzumab has shown promising results in clinical trials as monotherapy for achieving durable remissions. In addition, unlike previous treatments that require long-term continuous administration and hospitalization, the treatment period is predetermined, so it is expected to reduce the burden of hospital visits associated with treatment. We will continue working with the authorities to deliver this drug, which has the potential to change patients’ prognosis and social life, for patients as quickly as possible," said Dr. Osamu Okuda, Chugai’s President and CEO.

The application is based on the results of the Japanese phase I study and overseas Phase I/II study conducted by Roche in patients with R/R FL who had previously received two or more prior systemic therapies.

On March 14, 2024 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it filed regulatory application with the Ministry of Health, Labour and Welfare for the anti-cancer agent/humanized anti-PD-L1 monoclonal antibody Tecentriq Intravenous Infusion 1200 mg [generic name: atezolizumab (genetical recombination)] for an additional indication of alveolar soft part sarcoma (Press release, Chugai, MAR 14, 2024, View Source [SID1234641158]).

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!

"Alveolar soft part sarcoma, which is very common and most common in the adolescents and young adults (AYA) generation and very rare, is known to have a poor prognosis with no standard treatment if it becomes unresectable. We are working to obtain approval so that Tecentriq, a cancer immunotherapy that demonstrated favorable efficacy, can be delivered to patients as soon as possible as a new therapeutic option for alveolar soft part sarcoma," said Chugai’s President and CEO, Dr. Osamu Okuda.

This filing is based on the results from a phase II ALBERT study initiated by investigators in Japan including National Cancer Center Hospital and an overseas phase II clinical study conducted by the National Cancer Institute (NCI), which evaluated the efficacy and safety of Tecentriq in patients with unresectable alveolar soft part sarcoma.

Chugai Pharmaceutical, a leading company in the oncology field, remains committed to addressing unmet medical need in cancer treatment with innovative medicines for patients and healthcare professionals.

About ALBERT study1
ALBERT study is a Phase II, multicenter, open-label, single-arm study led by physicians including National Cancer Center Hospital to evaluate the efficacy and safety of Tecentriq in patients with unresectable alveolar soft part sarcoma. The study enrolled 20 patients to investigate safety and efficacy. The primary endpoint is overall response rate. Major secondary endpoints include progression-free survival, overall survival, and safety.

ALBERT study is being conducted as a substudy of the MASTER KEY project, which promotes the development of treatments for rare cancers through industry-academia collaboration with the National Cancer Center Hospital.

About alveolar soft part sarcoma2,3
Alveolar soft part sarcoma is an ultra-rare cancer accounting for less than 1% of soft tissue sarcomas. It is estimated to occur in 15-40 Japanese people annually. It most commonly affects the limbs, mainly the thighs, and is more common among adolescents and young adults (15-35 years old, AYA generation). Unresectable alveolar soft part sarcoma has a poor prognosis, and no standard treatment has been established.

About Tecentriq
Tecentriq is a cancer immune checkpoint inhibitor targeting PD-L1, which is a protein expressed on tumor and tumor-infiltrating immune cells. PD-L1 blocks T cell activity by binding with PD-1 and B7.1 receptors on T cell surface. By inhibiting PD-L1, Tecentriq may enable the activation of T cells and boost immune response against cancer cells. In Japan, Tecentriq was launched in April 2018 and has obtained approval for 4 indications (extensive-stage small cell lung cancer, non-small cell lung cancer, breast cancer, and hepatocellular carcinoma).

Trademarks used or mentioned in this release are protected by law.

Sources

An investigator-initiated clinical study conducting in patients with alveolar soft part sarcoma aged 16 years or older, with the aim of obtaining regulatory approval for the first immune checkpoint inhibitor for sarcoma and accelerating the development of new treatments for rare cancers and generation AYA patients (Press release by National Cancer Center Hospital in Japan on November 5, 2020). View Source (accessed in March 2024)
The Japanese Orthopaedic Association. Clinical Practice Guideline for Soft Tissue Tumor 2020 Revised Version 3. Nankodo
Paoluzzi L, Maki RG. Diagnosis, Prognosis, and Treatment of Alveolar Soft-Part Sarcoma: A Review. JAMA Oncol. 2019;5(2):254-260.