On November 28, 2023 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported program updates for pan-RAF inhibitor naporafenib and central nervous system (CNS)-penetrant EGFR inhibitor ERAS-801, as well as a strategic program prioritization that extends its projected cash runway from H2 2025 to H1 2026 (Press release, Erasca, NOV 28, 2023, View Source [SID1234639351]).

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"We are excited about the recent progress across key clinical programs, including the regulatory alignment with U.S. and European health authorities for our global naporafenib registrational trial which is on track to initiate in the first half of 2024, the establishment of the maximum tolerated dose (MTD) for ERAS-801 in patients with glioblastoma (GBM), and the promising preliminary activity of ERAS-007 plus encorafenib and cetuximab (EC) in EC-naïve patients with BRAF mutant colorectal cancer (CRC) presented at ASCO (Free ASCO Whitepaper)," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "To further maximize resources, we have strategically refined our pipeline to focus on programs with the greatest therapeutic potential for patients with high unmet needs using a data-driven approach. As such, we are deprioritizing our ERAS-601 clinical trial (FLAGSHP-1) and our preclinical ERAS-5 ULK inhibitor and ERAS-10 protein degrader programs. Importantly, this pipeline prioritization extends our cash runway into the first half of 2026 and through key milestones, including important clinical trial readouts for naporafenib, ERAS-801, and ERAS-007."

Recent Program Updates

Naporafenib Plus Trametinib for Patients with NRAS mutant (NRASm) Melanoma in Pivotal SEACRAFT-2 Trial
End of Phase 2 meetings with U.S. Food and Drug Administration (FDA) and European health authorities confirm SEACRAFT-2 Phase 3 trial design and provide clarity on registrational pathway:

Enrollment of patients with high unmet medical need who progressed on, or are intolerant to, standard of care immune checkpoint inhibitor therapy
Comparator arm is physicians’ choice of cytotoxic chemotherapy or trametinib
Dual primary endpoint evaluation of progression free survival (PFS) and overall survival (OS), with PFS acceptable for potential initial approval
The Phase 3 trial consists of two stages: a randomized, controlled, dose optimization stage, for which we expect to have a data readout in 2025, and a randomized, controlled stage to support regulatory approval
Phase 3 SEACRAFT-2 trial initiation remains on track for H1 2024
ERAS-801 for Patients with Recurrent GBM in Phase 1 THUNDERBBOLT-1 Trial
Thirty-three patients with recurrent glioblastoma (rGBM) were enrolled in seven dose escalation cohorts. ERAS-801 monotherapy has been granted Orphan Drug and Fast Track Designations (ODD and FTD) by the FDA. Interest in THUNDERBBOLT-1 from trial investigators continues to be robust.

MTD identified as 240 mg once a day (QD) and MTD-1 identified as 160 mg QD for ERAS-801
ERAS-801 was safe and tolerable at the MTD and MTD-1 dose levels. The adverse event profile was consistent with the mechanism of action and observations in non-clinical studies
ERAS-801 exhibited well behaved pharmacokinetic (PK) characteristics: ERAS-801 showed rapid absorption and had dose-dependent increases in PK exposure. Steady-state PK exposures at doses of 160 mg QD and above exceeded the concentration at which 90% tumor growth inhibition was achieved in the GBM patient-derived orthotopic xenograft (PDOX) mouse model.
Expansion cohorts actively enrolling to collect additional safety, tolerability, and preliminary efficacy data to support dose optimization and selection
Phase 1 dose escalation data to be presented at a scientific meeting in H1 2024; expansion cohort data are anticipated in H2 2024
Shannon R. Morris, M.D., Ph.D., Erasca’s chief medical officer, added, "ERAS-801 is an orally bioavailable CNS-penetrant EGFR inhibitor specifically designed to target the unique EGFR alterations observed in GBM, initially as a monotherapy treatment. Identification of the MTD signals the transition of ERAS-801 to the next stage of development with a focus on characterizing the clinical activity of the molecule in patients with EGFR-amplified rGBM, who may achieve maximum benefit from treatment. Notably, this population represents nearly half of all patients with GBM and 85% of all patients with EGFR-altered GBM."

Prioritized Clinical Programs and Key Upcoming Milestones
Naporafenib – Pan-RAF Inhibitor

Dosing of the first patient in pivotal Phase 3 SEACRAFT-2 trial in patients with NRASm melanoma expected H1 2024
Initial signal-seeking Phase 1b efficacy data in relevant tumor types from patients with RAS Q61X solid tumors in ongoing SEACRAFT-1 trial expected between Q2-Q4 2024
ERAS-801 – CNS-penetrant EGFR Inhibitor

Phase 1 monotherapy dose escalation and expansion data in rGBM expected in 2024
ERAS-007 – ERK1/2 Inhibitor

Initial dose expansion data from Phase 1b/2 HERKULES-3 trial further evaluating encouraging early efficacy data with ERAS-007 in combination with EC in EC-naïve patients with BRAF mutant CRC expected between H2 2023 and H1 2024
Deprioritized Opportunities
Select trials or programs were deprioritized, despite their potential differentiation, to focus the company’s resources on the most promising programs, which is expected to extend the company’s cash runway from H2 2025 to H1 2026:

FLAGSHP-1 – Phase 1b combination trial of ERAS-601 SHP2 inhibitor with cetuximab was deprioritized. Though ERAS-601 achieved confirmed responses as a monotherapy and in combination with cetuximab, preliminary data do not justify further development of this combination in FLAGSHP-1 indications
ERAS-5 – Preclinical ULK inhibitor
ERAS-10 – Preclinical protein degrader

On November 28, 2023 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers harboring ESR1 mutations, reported that it had five abstracts accepted as poster presentations at the 2023 San Antonio Breast Cancer Symposium (SABCS), which will be held Dec. 5-9 at the Henry B. Gonzalez Convention Center in San Antonio (Press release, Sermonix Pharmaceuticals, NOV 28, 2023, View Source [SID1234638047]).

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Three posters delve into clinical data tied to Sermonix’s Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) studies. One assesses baseline genomic alterations and the activity of lasofoxifene, Sermonix’s investigational novel endocrine therapy, and Eli Lilly and Company’s CDK4/6 inhibitor abemaciclib during the ELAINE-2 study. A second poster addresses pharmacokinetics of lasofoxifene as a monotherapy and in combination with abemaciclib. The third poster is a trial-in-progress update on ELAINE-3, which is studying the efficacy and safety of lasofoxifene in combination with abemaciclib in treating locally advanced or ER+/HER2- mBC with an ESR1 mutation.

The other two posters address the results of Sermonix’s third ESR1 and Quality of Life Survey (EQUALS 3), which was developed to help inform practicing oncologists about patients’ understanding of ESR1 mutations and the quality of life for metastatic breast cancer (mBC) patients. One poster addresses patient-provider communication challenges with respect to side effects of mBC treatments, and the second discusses how minimizing treatment toxicity and side effects impacts quality of life for ER+/HER2- mBC patients.

"Sermonix looks forward to updating our peers at SABCS 2023 about our growing understanding of lasofoxifene as a monotherapy and combination therapy, our initiated ELAINE-3 study, and our continuing work to learn more about how metastatic breast cancer impacts patient quality of life," said Dr. David Portman, Sermonix founder and chief executive officer. "We are committed to investigating lasofoxifene’s efficacy in combating metastatic breast cancer, as well as observing its impacts on vaginal and sexual health, all issues that affect patients greatly."

Poster sessions details are as follows:

Poster Title: Baseline genomic alterations and the activity of lasofoxifene (LAS) plus abemaciclib (Abema) in patients with ER+/HER2- metastatic breast cancer (mBC): the ELAINE-2 study
Poster ID: P02-14-09
Date: Wednesday, Dec. 6, 2023
Time: 5-7 p.m. CT
Poster Title: Pharmacokinetics (PK) of lasofoxifene (LAS) monotherapy and combined with abemaciclib (Abema)
Poster ID: P03-18-05
Date: Thursday, Dec. 7, 2023
Time: 12-2 p.m. CT
Poster Title: Trial in progress: Open-label, randomized, multicenter, phase 3, ELAINE-3 study of the efficacy and safety of lasofoxifene plus abemaciclib for treating locally advanced or ER+/HER2- metastatic breast cancer with an ESR1 mutation
Poster ID: P01-18-12
Date: Wednesday, Dec. 6, 2023
Time: 12-2 p.m. CT
Poster Title: Patient (pt)-provider communication challenges about side effects/ from metastatic breast cancer (mBC) treatments]
Poster ID: P03-12-05
Date: Thursday, Dec. 7, 2023
Time: 12-2 p.m. CT
Poster Title: Minimization of treatment toxicity/side effects and their impact on quality of life (QoL) in patients (pts) with ER+/HER2- metastatic breast cancer (mBC)
Poster ID: P03-12-06
Date: Friday, Dec. 8, 2023
Time: 12-2 p.m. CT
To learn more about Sermonix Pharmaceuticals and lasofoxifene, visit View Source For more information about the ELAINE studies, visit View Source

About Lasofoxifene
Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

On November 28, 2023 Ribometrix, a biotechnology company developing small molecule therapeutics that modulate RNA biology, reported that it will present preclinical data showing anti-tumor benefit of eIF4E inhibition in Estrogen Receptor-positive (ER+) breast cancer at the annual San Antonio Breast Cancer Symposium, held December 5-9, 2023, in San Antonio, TX (Press release, Ribometrix, NOV 28, 2023, View Source [SID1234638045]).

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Ribometrix is evaluating its portfolio of inhibitors targeting eIF4E in preclinical studies in cancer, including melanoma and breast cancer. eIF4E is both a potent oncogene and a regulator of resistance to therapies targeting common oncogenic drivers, and Ribometrix’s data support the potential efficacy of its eIF4E inhibitors alone or in combination with standard-of-care in treatment naïve and treatment-resistant settings.

Presentation Details
Abstract Title: Pharmacological eIF4E inhibition suppresses anti-tumor activity in ER+ breast cancer
Abstract: PO5-27-09
Presenter: Matthew Friedersdorf, Ph.D., Associate Director, Translational Medicine at Ribometrix
Session: Poster Session 5
Date:  Friday, December 8, 2023
Time:  12:00pm – 2:00pm CT

At the time of presentation, Ribometrix’s poster will be made available on the "Publications" page of the "News" section of its website.

About eIF4E
Eukaryotic translation initiation factor 4E (eIF4E), the main regulatory component of cap-dependent mRNA translation, selectively promotes pro-oncogenic protein synthesis in response to activation of multiple tumor signaling pathways. Interestingly, many pro-oncogenic signaling pathways require eIF4E activity to promote tumor growth. Clinically, eIF4E activity is elevated in many tumor indications and it is typically associated with poor prognosis. Thus, targeting eIF4E has the potential to enhance anti-cancer activity when given in combination with standard-of-care. Additionally, eIF4E is also central to many resistance mechanisms, therefore eIF4E inhibition has the potential to overcome drug resistance and re-sensitize tumors to anti-cancer therapies. Ribometrix is developing eIF4E inhibitors as a promising therapeutic strategy to inhibit oncogene expression to enhance efficacy in combination and overcome resistance to targeted anti-cancer therapies.

On November 28, 2023 AstraZeneca reported that it will present new clinical and real-world data in multiple haematological conditions at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, CA, 9 to 12 December 2023 (Press release, AstraZeneca, NOV 28, 2023, View Source [SID1234638029]).

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A total of 63 abstracts will feature 14 approved and potential new medicines across the Company’s portfolio and pipeline including from Alexion, AstraZeneca’s Rare Disease group, in chronic lymphocytic leukaemia (CLL) and several types of lymphoma, paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uraemic syndrome (aHUS) and amyloid light-chain (AL) amyloidosis.

Anas Younes, Senior Vice President, Haematology R&D, AstraZeneca, said: "Our data at ASH (Free ASH Whitepaper) will exemplify how we are advancing a range of innovative modalities including antibody drug conjugates, next-generation immunotherapies and T-cell engagers in haematology. Updated clinical data for AZD0486, our CD19/CD3 T-cell engager, reinforce our belief in this approach as a potential new treatment for lymphoma, and new Calquence data continue to demonstrate long-term efficacy and safety in chronic lymphocytic leukaemia with further follow up."

Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety, Alexion, said: "Alexion has transformed the treatment landscape and redefined care for the paroxysmal nocturnal haemoglobinuria patient community over the past two decades. At the ASH (Free ASH Whitepaper) Annual Meeting, new results from our pivotal ALPHA trial will demonstrate the promise of Factor D inhibition to advance care for the small subset of patients with paroxysmal nocturnal haemoglobinuria who experience clinically significant extravascular haemolysis. We are proud to further our leadership in rare disease by sharing data from our robust haematology pipeline, reflecting our commitment to innovation and improving outcomes for the patients and families we serve."

Calquence continues to demonstrate long-term benefits in CLL

Six-year follow-up data from the pivotal ELEVATE-TN Phase III trial will further support the continued efficacy, safety and tolerability of Calquence for long-term use in patients with treatment-naïve CLL.1

Data from a Phase II trial will show the safety and efficacy of Calquence and rituximab followed by chemotherapy and autologous stem cell transplantation in fit patients with treatment-naïve mantle cell lymphoma (MCL).2

An analysis of five prospective Calquence trials, including three randomised, controlled Phase III trials and two non-randomised trials, will show acceptable safety outcomes based on rates of nonfatal and fatal ventricular arrhythmias and sudden death in patients with CLL.3

Novel early assets show potential to improve outcomes for blood cancer patients

Data from our early portfolio will demonstrate how the Company is advancing multiple modalities across several scientific platforms, including Immuno-Oncology, Immune-Engagers, Antibody Drug Conjugates (ADCs) and Epigenetics as part of its strategy to attack cancer from multiple angles.

Updated Phase I data for AstraZeneca’s CD19/CD3 T-cell engager, AZD0486, will further demonstrate the acceptable safety profile and high response rate of this treatment in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL).4 We will also present the first clinical data on sabestomig, a PD-1/TIM-3 targeting bispecific antibody, in R/R Hodgkin lymphoma, showing encouraging early signals of activity.5

The first preclinical data for AZD9829, a novel CD123-targeting ADC, using AstraZeneca’s proprietary linker technology to deliver a topoisomerase I inhibitor warhead, will demonstrate promising anti-tumour activity in acute myeloid leukaemia.6 In addition, preclinical data will demonstrate anti-tumour activity of AstraZeneca’s novel PRMT5 inhibitor in MTAP silenced Hodgkin lymphoma models.7

Showcasing advances to bolster our leadership in PNH with new data on Factor D inhibition and impact of C5 inhibition in long-term disease control

New results from the 24-week and long-term extension period from the pivotal ALPHA Phase III trial will reinforce the potential for danicopan add-on therapy to address clinically significant extravascular haemolysis (EVH) in the small subset of PNH patients who experience this condition while treated with C5 inhibitor therapy, allowing them to maintain control of intravascular haemolysis (IVH) through standard-of-care treatment with Ultomiris (ravulizumab) or Soliris (eculizumab).8

Further, patient-reported outcomes from the ALPHA trial will suggest danicopan as an add-on to Ultomiris or Soliris improved quality of life compared to C5 inhibitor therapy alone in patients with PNH who experience clinically significant EVH.9

Additionally, Alexion will present an analysis of six-year outcomes from the Phase III clinical trial evaluating the safety and efficacy of Ultomiris in patients with PNH who did not have previous treatment with a C5 inhibitor.10 The analysis compared survival against untreated patients in the International PNH Registry, the largest global real-world database of patients with PNH. Results will suggest Ultomiris improved survival and maintained effective long-term control of IVH, the most significant contributor to morbidity and premature mortality in PNH.10

Improving diagnosis and management of life-threatening rare diseases, including amyloidosis

24-month results of a Phase II trial will demonstrate the safety and tolerability of CAEL-101 in combination with cyclophosphamide-bortezomib-dexamethasone with or without daratumumab for the treatment of AL amyloidosis.11

Real-world analyses across AL amyloidosis, aHUS and haematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) will also be presented, advancing the scientific understanding of these rare, haematological conditions.12-16

Key presentations during the 65th ASH (Free ASH Whitepaper) Annual Meeting and Exposition

Lead author

Abstract title

Presentation details

Calquence (acalabrutinib)
Sharman, JP

Acalabrutinib ± Obinutuzumab vs Obinutuzumab + Chlorambucil in Treatment-naive Chronic Lymphocytic Leukemia: 6-year Follow-up of ELEVATE-TN

Abstract # 636

Oral Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Frontline Treatment with Targeted Agents in Patients with Chronic Lymphocytic Leukemia

10 December 2023

17:45 PST

Location: Seaport Ballroom ABCD (Manchester Grand Hyatt San Diego)

Westin, J

Smart Stop: Lenalidomide, Tafasitamab, Rituximab and Acalabrutinib Alone and with Combination Chemotherapy for the Treatment of Newly Diagnosed Diffuse Large B-cell Lymphoma

Abstract # 856

Oral Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Initial treatment strategies in Aggressive B-Cell Lymphomas

11 December 2023

15:30 PST

Location: Seaport Ballroom ABCD (Manchester Grand Hyatt San Diego)

Hawkes, EA

A Window Study of Acalabrutinib and Rituximab, Followed by Chemotherapy and Autograft (ASCT) in Fit Patients with Treatment-naïve Mantle Cell Lymphoma (MCL): First Report of the Investigator-initiated Australasian Leukaemia and Lymphoma Group NHL33 ‘WAMM’ Trial

Abstract # 735

Oral Session: 623. Mantle Cell, Follicular and Other Indolent B-Cell Lymphomas: Clinical and Epidemiological: Prospective Clinical Trials in Mantle Cell Lymphoma Incorporating Novel Agents

11 December 2023

11:00 PST

Location: Grand Hall B (Manchester Grand Hyatt San Diego)

Hawkes, EA

TrAVeRse: A Phase 2, Open-Label, Randomized Study of Acalabrutinib in Combination with Venetoclax and Rituximab in Patients with Treatment- naïve Mantle Cell Lymphoma

Abstract # 3054

Poster Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphomas: Clinical and Epidemiological: Poster II

10 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

Sharman, J

Analysis of Ventricular Arrhythmias and Sudden Death with Acalabrutinib From 5 Prospective Clinical Trials

Abstract # 4643

Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III

11 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

Ferrajoli, A

Cumulative Review of Hypertension in Patients with Chronic Lymphocytic Leukemia (CLL) and Other Hematologic Malignancies Treated with Acalabrutinib: Data from Clinical Trials

Abstract # 1917

Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I

9 December 2023

17:30 – 19:30 PST

Location: Halls G-H (San Diego Convention Center)

Sun, C

Extended Follow-Up and Resistance Mutations in CLL Patients Treated with Acalabrutinib

Abstract # 1891

Poster Session: 641. Chronic Lymphocytic Leukemias: Basic and Translational: Poster I

9 December 2023

17:30 – 19:30 PST

Location: Halls G-H (San Diego Convention Center)

Jain, P

Acalabrutinib with Rituximab as First-line Therapy for Older Patients with Mantle Cell Lymphoma – A Phase II Clinical Trial

Abstract # 3036

Poster Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphomas: Clinical and Epidemiological: Poster II

10 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

Perini, G

ACRUE: A Phase 2, Open-label Study of Acalabrutinib in Combination with Rituximab in Elderly and/or Frail Patients with Treatment-naïve Diffuse Large B-Cell Lymphoma

e-Publication

Online Only

AZD0486
Gaballa, S

Double Step-Up Dosing (2SUD) Regimen Mitigates Severe ICANS and CRS While Maintaining a High Efficacy in Subjects with Relapsed/Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) Treated with AZD0486, a Novel CD19xCD3 T-cell Engager (TCE): Updated Safety and Efficacy Data from the Ongoing First-in-Human (FIH) Phase I Trial

Abstract # 1662

Poster Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphomas: Clinical and Epidemiological: Poster I

9 December 2023

17:30 – 19:30 PST

Location: Halls G-H (San Diego Convention Center)

AZD9829

Dutta, D

First Disclosure of AZD9829, a TOP1i-ADC Targeting CD123: Promising Preclinical Activity in AML Models with Minimal Effect on Healthy Progenitors

e-Publication

Online Only

AZD7789

Mei, M

Safety and Preliminary Efficacy of Sabestomig (AZD7789), an Anti-PD-1 and Anti-TIM-3 Bispecific Antibody, in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma Previously Treated with Anti-PD-(L)1 Therapy

Abstract # 4433

Poster Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological: Poster III

11 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

PRMT5 inhibitor

Urosevic, J

Epigenetic Silencing of MTAP in Hodgkin’s Lymphoma Renders it Sensitive to a 2nd Generation PRMT5 Inhibitor

Abstract # 4185

Poster Session: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster III

11 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

Danicopan

Kulasekararaj, A

Danicopan as Add-On Therapy to Ravulizumab or Eculizumab Versus Placebo in Patients with Paroxysmal Nocturnal Hemoglobinuria and Clinically Significant Extravascular Hemolysis: Phase 3 Long-term Data

Abstract # 576

Oral Session: 508. Bone Marrow Failure: Acquired: Unraveling the Future of PNH Therapy from Clinical Trials

10 December 2023

17:45 PST

Location: Room 7 (San Diego Convention Center)

Piatek, C

Patient-reported Outcomes: Danicopan as Add-On Therapy to Ravulizumab or Eculizumab Versus Placebo in Patients with Paroxysmal Nocturnal Hemoglobinuria and Clinically Significant Extravascular Hemolysis

Abstract # 1346

Poster Session: 508. Bone Marrow Failure: Acquired: Poster I

9 December 2023

17:30 – 19:30 PST

Location: Halls G-H (San Diego Convention Center)

Ultomiris (ravulizumab)

Kulasekararaj, A

Ravulizumab Provides Durable Control of Intravascular Hemolysis and Improves Survival in Patients with Paroxysmal Nocturnal Hemoglobinuria: Long-Term Follow-Up of Study 301 and Comparisons with Patients of the International PNH Registry

Abstract # 2714

Poster Session: 508. Bone Marrow Failure: Acquired: Poster II

10 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

Röth, A

Ravulizumab Effectiveness in the Real-world: Evidence from the International PNH Registry

Abstract # 2722

Poster Session: 508. Bone Marrow Failure: Acquired: Poster II

10 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

Piatek, C

Efficacy and Safety of Subcutaneous Ravulizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria Who Received Prior Intravenous Eculizumab: 2-Year Follow-Up

Abstract # 2713

Poster Session: 508. Bone Marrow Failure: Acquired: Poster II

10 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

CAEL-101

Valent, J

Safety and Tolerability of CAEL-101, an Anti-Amyloid Monoclonal Antibody, Combined with Anti-Plasma Cell Dyscrasia Therapy in Patients with Light-Chain Amyloidosis: 24-Month Results of a Phase 2 Study

Abstract # 540

Oral Session: 654. MGUS, Amyloidosis and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: From Light Chain to Fibril–Novel Diagnostics to Treatments for Amyloidosis

10 December 2023

13:15 PST

Location: Seaport Ballroom EFGH (Manchester Grand Hyatt San Diego)

Costello, M

CAEL-101 Enhances the Clearance of Light Chain Fibrils and Intermediate Aggregates by Phagocytosis

Abstract # 3307

Poster Session: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Poster II

10 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

AL Amyloidosis

Lyons, G

Treatment Patterns and Outcomes for Patients with Light Chain (AL) Amyloidosis: Analysis of a Large US Claims Database

e-Publication

Online Only

Thompson, J

Real-world Treatment Patterns Following Update to National Comprehensive Cancer Network Guidelines for Light-Chain Amyloidosis: Results from a US Administrative Claims Database

e-Publication

Online Only

Laires, P

Prevalence, Incidence, and Characterization of Light Chain Amyloidosis in the USA: A Real-world Analysis Utilizing Electronic Health Records (EHR)

e-Publication

Online Only

aHUS

Wang, Y

Patient Characteristics and Diagnostic Journey of Thrombotic Microangiopathy Associated with a Trigger: A Real-world, Retrospective, Multi-national Study

e-Publication

Online Only

HSCT-TMA

Wang, Y

Real-world Analysis of the Underdiagnosis, Clinical Outcomes and Associated Burden of Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy (HSCT-TMA) in the United States of America

Abstract # 491

Oral Session: 904. Outcomes Research – Non-Malignant Conditions: What to Know: Management Costs and Outcomes in Various Non-Malignant Disorders

10 December 2023

10:30 PST

Location: Pacific Ballroom Salons 15-17 (Marriott Marquis San Diego Marina)

PNH

Wagner-Ballon, O

Neutrophil PNH Type II Cells Are Associated with Thrombosis and Bone Marrow Failure Without Hemolysis: Evidence from Analysis of the 5-year French Nation-Wide Multicenter Observational Study

Abstract # 4083

Poster Session: 508. Bone Marrow Failure: Acquired: Poster III

11 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

On November 28, 2023 TME Pharma N.V. (Euronext Growth Paris: ALTME), a biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported the launch of a 100% guaranteed capital increase through issuance of new shares for €2.7 million gross proceeds with associated warrants potentially raising up to €2.2 million of additional gross proceeds in order to secure financing to reach key regulatory milestones in 2024 (Press release, TME Pharma, NOV 28, 2023, View Source [SID1234638028]). The guaranteed amount is secured by a group of Dutch investors.

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The capital increase is carried out with preferential subscription rights for the company’s shareholders. The preferential subscription rights are detached and their listing begins today, November 28, 2023 (ISIN code of PSR: FR001400M9E2).

The transaction is expected to extend the company’s cash runway from February 20241 into May 2024 with possibility to extend further into July 2024 if the associated warrants expiring in February 2024 are exercised in full, and to September 2024 if both sets of warrants are fully exercised by July 2024. This transaction will reduce the liquidity risk that the company has been facing in recent months. The operation offers current shareholders subscription rights to maintain their holding in the company without being diluted.

"This guaranteed capital injection provides TME Pharma with financing into May 2024, with the possibility of extending our cash runway even further should all the warrants be fully exercised while ensuring minimal dilution to existing shareholders who continue to support our venture," said Aram Mangasarian, CEO of TME Pharma. "This will allow us to achieve our next clinical and regulatory milestones with our lead asset NOX-A12 in newly diagnosed brain cancer patients, including further maturing of the survival data, an Investigational New Drug filing, and potential access to expedited regulatory pathways in the US, such as Fast-Track. We are also announcing the repurchase of almost half our existing outstanding convertible debt, with the remainder locked up until April next year. This is the latest step in our commitment to our shareholders to end the use of convertible bond financing so we can remain focused on our goal of developing novel therapies for cancer patients and bringing them to market."

Key Preferential Rights Issue details2:

Preferential subscription right: 1 preferential subscription right (PSR) will be awarded for 1 ordinary share held on November 27, 2023
Subscription rate: Each 3 PSRs give right to subscribe for 5 ABSA Y (5 new shares with 5 Warrants Y attached)
Subscription price: €0.25 per ABSA Y, representing a 37.5% discount vs. the closing price of EUR 0.4005 of the company’s shares on November 24, 2023
Subscription period: From November 30 to December 11, 2023 (inclusive)
ABSA are shares with warrants attached. There are two types of ABSA: ABSA Y, containing one new share and one Warrant Y, and ABSA Z, containing one new share and one Warrant Z.

Warrants Y:

Each series of 5 Warrants Y entitle a holder to subscribe for 2 ABSA Z (2 new shares with 2 Warrants Z attached)
Warrant Y will have an exercise price of €0.25
Warrant Y maturity: February 16, 2024, with two periods of exercise. Warrants Y that have not been exercised by the end of the exercise period will become null and void. See Warrants Terms & Conditions for further details.
Warrants Z:

Each series of 4 Warrants Z entitle a holder to subscribe for 5 new shares
Warrant Z will have an exercise price of €0.20
Warrant Z maturity: June 30, 2025, with one period of exercise per quarter. Warrants Y that have not been exercised by the end of the exercise period at the latest will become null and void, without value. See Warrants Terms & Conditions for further details.
Illustrative example

A shareholder holding 300 shares of TME Pharma as of November 27, 2023, would be awarded 300 preferential subscription rights (PSRs). Having 300 PSRs entitles the shareholder to acquire 500 ABSA Y, composed of 500 new shares and 500 Warrant Y, for an amount of €125. The 500 Warrant Y entitle them to subscribe for 200 ABSA Z for €50. These 200 ABSA Z are composed of 200 new shares and 200 Warrant Z. The 200 Warrant Z can be exercised for €50 granting 250 new TME Pharma shares. Thus, if this shareholder participates fully in the transaction, they would hold 1250 shares, of which 900 newly acquired for €225.

Timetable of the Rights Issue:

November 17, 2023

Decision of the Board of Directors on the launch of Capital Increase

November 24, 2023

Press release announcing the Capital Increase
Release of the Euronext notice

November 27, 2023

Suspension of the right to exercise dilutive instruments issued by the Company
Accounting day at the end of which the holders of existing shares recorded in their securities accounts will be awarded preferential subscription rights (PSRs)

November 28, 2023

Detachment of PSRs and start of their listing

November 29, 2023

Euronext "Record date"

November 30, 2023

(included)

Opening of the subscription period – Start of the period of PSR exercise

December 07, 2023 (included)

End of PSR listing

December 11, 2023 (included)

Closing of the subscription period – End of the period of PSR exercise

December 13, 2023

Reception of the results of the public offer

December 14, 2023

Decision of the Board of Directors on the issue of the New Shares, and where applicable, the limitation of the Capital Increase, the reallocation of the Capital Increase

December 14, 2023

Distribution of the press release announcing the final amount of Capital Increase

December 18, 2023

Settlement-delivery, listing of New Shares, listing of Warrants Y

December 18, 2023

Resumption of the right to exercise any dilutive instruments issued by the Company, except convertible bonds subject to lock-up until April 1, 2024

Use of Proceeds:

Approximately 1/3rd of the proceeds from the guaranteed part of the capital increase will be used to reach increased data maturity in the ongoing NOX-A12 GLORIA Phase 1/2 trial in glioblastoma, advance the discussions with the US Food and Drug Administration (FDA) past regulatory milestones. Another 1/3rd of proceeds will be used for general corporate purposes including intensifying interactions with investors and potential industry partners. The final 1/3rd will be used to buy back part of the remainder of the convertible debt as described below.

Management believes that the completion of the regulatory milestones with the FDA in Q1-2024 will allow the company to pursue additional non-dilutive and dilutive financing on improved conditions.

Buyback and Lock-up of Convertible Debt key details3:

The company plans to reduce the outstanding convertible debt with part of the guaranteed proceeds from this transaction. As announced on April 18, 2023, the company terminated the agreement with Atlas Special Opportunities, LLC (ASO) other than with regard to already issued convertible bonds (CBs). One of the conditions of the investor group guaranteeing this financing is that TME Pharma repurchase 898 out of 1,898 outstanding convertible bonds for the total amount of €942,900 including 5% premium4 representing approximately 1/3rd of the initial guaranteed part of the funds raised. Furthermore, ASO agrees to a lock-up of the remaining 1,000 convertible bonds until April 1, 2024, in exchange for a flat fee of 100 additional CBs with a nominal value of €100,000. The redemption and lock-up prevent further conversion of CBs to shares and reiterate the company’s commitment to methodically end its reliance on convertible bond financing. The company is evaluating options to repurchase the last part of remaining convertible debt.

Guarantee:

The capital increase of €2.7 million is guaranteed by a group of four investors, whose individual commitment is not representing a concerted action towards the potential control of the company. None of them individually would cross threshold of 50% ownership even if the guarantee was required in full.

Shareholder and Corporate Authorizations:

The issuance of shares in this transaction relies upon the authorizations granted to the Issuer by its shareholders in the annual general meeting (AGM) on June 29, 2023. Issuer has completed and obtained all necessary corporate approvals for the rights issue. In particular, at the AGM held on 29 June 2023, the company’s shareholders approved the authorized capital amounting to € 212,500, divided into 20,000,000 ordinary shares, and 1,250,000 preference shares, each share with a nominal value of € 0.01. In addition, and if and as per the moment the company’s issued and paid-up ordinary share capital will amount to €200,000, comprised 20,000,000 ordinary shares, the transitional provision outlined in article 37 of the company’s articles of association will become effective, according to which the authorized capital of the company amounts to € 900,000 divided into 80,000,000 ordinary shares and 10,000,000 preference shares, each share with a nominal value of € 0.01.

Dilutive Potential:

Shareholders participating fully in the transaction, i.e. purchasing the ABSA Y and exercising Warrants Y and Z will not be diluted, and may increase their percentage shareholding if other investors do not exercise their Warrants.

Table: Dilutive Potential from Transaction Assuming an Existing Shareholder Does NOT Participate in the Transaction

Description

Shares to be issued
(max)

Total shares
outstanding

Dilution (max)

Shareholder
starting with 1%
would then hold

Purchase of ABSA Y

10,825,528

17,320,845

62.50%

0.38%

Exercise of Warrant Y

4,330,211

21,651,057

70.00%

0.30%

Exercise of Warrant Z

5,412,764

27,063,821

76.00%

0.24%

Risk Factors:

The main risk factors relating to the issue are as follows:

the market for preferential subscription rights may offer only limited liquidity and be subject to a high level of volatility;
shareholders who do not exercise their preferential subscription rights would see their stake in the company’s share capital diluted;
the market price of the company’s shares may fluctuate and fall below the subscription price of the New Shares;
the volatility and liquidity of the company’s shares may fluctuate significantly;
if the market price of the company’s shares falls, the value of preferential subscription rights could fall;
the Rights Issue is not subject to a performance guarantee and investors who have acquired preferential subscription rights could sustain a loss equal to the price of acquiring these preferential subscription rights.
The company expects to incur losses for the foreseeable future and will need substantial additional funding in order to complete the development and commercialization of its product candidates, which may not be available on acceptable terms when needed, if at all.
Before deciding to invest, Investors are asked to familiarise themselves with the risks described in the company’s 2022 annual financial report (LINK), and 2023 half-year financial report (LINK), both available on the company website. Key strategic, operational and financial risks are described in the Information Document prepared specifically for this transaction in accordance with the guidelines of the Dutch Authority for the Financial Markets which is available on the company website (LINK).

Potential Conflict of Interest:

Part of the variable remuneration of management relates to corporate goals for advancing the development pipeline of TME Pharma as well as securing the respective funding.

Additional Information:

Additional Information: The characteristics, terms and conditions and dilution resulting from the transaction may be found in the Annex to this press release and in the dedicated Right Issue page on the TME Pharma website: LINK.