Verastem Oncology Reports Fourth Quarter and Full Year 2023 Financial Results and Highlights Recent Business Updates

On March 14, 2024 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported financial results for the three months and full year ended December 31, 2023, and highlighted recent progress (Press release, Verastem, MAR 14, 2024, View Source [SID1234641181]).

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"In 2023, we made significant progress toward expanding the opportunities for avutometinib combination therapies across RAS/MAPK driven cancers and I am extremely proud of the team’s accomplishments," said Dan Paterson, president and chief executive officer of Verastem Oncology. "2024 is expected to be a pivotal year with the planned NDA submission for our avutometinib and defactinib combination in recurrent LGSOC, and multiple clinical data readouts across our programs including initial data from the RAMP 205 trial in metastatic pancreatic cancer and data from the combination with G12C inhibitors in NSCLC. We look forward to continuing to deliver results across our programs."

Fourth Quarter 2023 and Recent Highlights

Avutometinib and Defactinib Combination in Low-Grade Serous Ovarian Cancer (LGSOC)

Initiated international confirmatory Phase 3 RAMP 301 trial evaluating the avutometinib and defactinib combination versus standard of care chemotherapy or hormonal therapy for the treatment of recurrent LGSOC in December 2023 to support potential full approval.
Reported results of a planned subgroup analysis of Part A of the Phase 2 RAMP 201 trial evaluating avutometinib and defactinib combination in recurrent LGSOC, which demonstrated promising efficacy in patients regardless of number and class of prior therapies including after poor response to prior therapy at the Annual Global Meeting of the International Gynecologic Cancer Society meeting in November 2023.
Launched patient and healthcare professional programs, including Let’s Talk About LGSOC, to support clinicians in the diagnosis and management of LGSOC and provide information and resources to patients.
Received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) in March 2024 for avutometinib alone or in combination with defactinib for the treatment of all patients with recurrent LGSOC.
Verastem anticipates the following milestones for avutometinib and defactinib combination in LGSOC in 2024:

On track to submit a rolling New Drug Application (NDA) for Accelerated Approval for the avutometinib and defactinib combination in LGSOC in H1 2024. Preparations for a potential U.S. commercial launch in 2025 are ongoing and plans to initiate discussions with European and Japanese regulatory authorities to address patient needs outside the U.S. continue to advance.
Plan to announce updated topline data from RAMP 201 trial in LGSOC in H1 2024.
Avutometinib in Combination with KRAS G12C Inhibitors in Non-Small Cell Lung Cancer (NSCLC)

Received Fast Track designation from the FDA for avutometinib, in combination with Amgen’s G12C inhibitor, LUMAKRAS (sotorasib), for the treatment of patients with KRAS G12C-mutant metastatic NSCLC who have received at least one prior systemic therapy and have not been previously treated with a KRAS G12C inhibitor, in January 2024.
Presented initial results from Phase 1/2 RAMP 203 trial evaluating the efficacy and safety of avutometinib and sotorasib in patients with KRAS G12C-mutant NSCLC who have or have not been previously treated with a KRAS G12C inhibitor at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in October 2023. The confirmed objective rate of response (ORR) was 25% with responses observed in both KRAS G12C inhibitor resistant and naïve patients, and a recommended Phase 2 dose was selected.
Added defactinib to RAMP 203 trial of avutometinib with sotorasib based on stronger tumor regressions in KRAS G12C-mutant NSCLC preclinical models when FAKi is added along with G12Ci + avutometinib.
Verastem anticipates the following milestones for avutometinib in combination with KRAS G12C inhibitors in 2024:

Data updates from patients with KRAS G12C-mutant NSCLC in the Phase 1/2 RAMP 203 trial evaluating avutometinib and sotorasib and the Phase 1/2 RAMP 204 trial evaluating avutometinib and adagrasib are planned for mid-2024.
Avutometinib and Defactinib Combination in Frontline Metastatic Pancreatic Cancer

Plan to present initial safety and efficacy results from RAMP 205 trial of avutometinib and defactinib in combination with current standard of care gemcitabine and nab-paclitaxel in frontline metastatic pancreatic cancer in H1 2024.
GFH375 (VS-7375): Oral KRAS G12D (ON/OFF) Inhibitor

Completed investigational new drug (IND)-enabling studies for oral KRAS G12D (ON/OFF) inhibitor GFH375 (VS-7375), the lead program in the collaboration with GenFleet Therapeutics ("GenFleet").
GenFleet is expected to submit an IND application for GFH375 (VS-7375) in China in H1 2024 with plans to begin a Phase 1 trial in H2 2024. Discovery/lead optimization continues for second and third programs.
Upcoming Presentations

Verastem previously announced the acceptance of multiple abstracts for presentation at upcoming medical conferences:

Multiple abstracts were selected for oral and poster presentations at the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer on March 16-18 in San Diego. These presentations will include a late-breaking oral presentation on a planned subgroup analysis of Part A of the Phase 2 RAMP 201 trial of avutometinib and defactinib combination of heavily pretreated patients with LGSOC and a plenary oral presentation of preclinical efficacy data of avutometinib in combination with a FAK inhibitor in recurrent LGSOC as well as a trials-in-progress poster about the Phase 3 RAMP 301 trial. See press release here.
Five preclinical data abstracts were accepted for poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 on April 5-10 in San Diego. These presentations will highlight anti-tumor efficacy data of GFH375 (VS-7375), data on RAF/MEK clamp avutometinib and FAK inhibition in pancreatic ductal adenocarcinoma models supporting the ongoing RAMP 205 trial, and avutometinib and a FAK inhibitor combination in cutaneous melanoma models to overcome resistance to BRAF and MEK inhibitors, resistance to immunotherapy, and brain metastasis. See press release here.
Corporate Updates

Strengthened the executive leadership team with appointments of Mike Crowther to Chief Commercial and Business Strategy Officer and the promotion of Dan Calkins to Chief Financial Officer in October 2023.
Fourth Quarter 2023 Financial Results

Verastem Oncology ended the fourth quarter of 2023 with cash, cash equivalents and investments of $137.1 million.

Total operating expenses for the three months ended December 31, 2023 (the "2023 Quarter") were $31.1 million, compared to $16.8 million for the three months ended December 31, 2022 (the "2022 Quarter").

Research & development expenses for the 2023 Quarter were $22.5 million, compared to $10.7 million for the 2022 Quarter. The increase of $11.8 million, or 110.3%, primarily resulted from increased contract research organization costs, increased drug substance and drug product costs, and increased personnel costs, including non-cash stock compensation.

Selling, general & administrative expenses for the 2023 Quarter were $8.6 million, compared to $6.1 million for the 2022 Quarter. The increase of $2.5 million, or 41.0%, was primarily related to increased personnel costs, including non-cash stock compensation, increased consulting and professional fees, and additional costs in anticipation of a potential launch of avutometinib and defactinib in LGSOC.

Net loss for the 2023 Quarter was $27.4 million, or $1.02 per share (basic and diluted), compared to a net loss of $16.8 million, or $0.99 per share (basic and diluted, each as adjusted for the Company’s reverse stock split), for the 2022 Quarter.

For the 2023 Quarter, non-GAAP adjusted net loss was $29.6 million, or $1.10 per share (diluted), compared to non-GAAP adjusted net loss of $15.4 million, or $0.90 per share (diluted, as adjusted for the Company’s reverse stock split), for the 2022 Quarter. Please refer to the GAAP to Non-GAAP Reconciliation attached to this press release.

Full-Year 2023 Financial Results

Total operating expenses for the year ended December 31, 2023 (the "2023 Period") were $92.1 million, compared to $75.5 million for the year ended December 31, 222 (the "2022 Period").

Research & development expenses for the 2023 Period were $61.4 million, compared to $50.6 million for the 2022 Period. The increase of $10.8 million, or 21.3%, was primarily related to increases in contract research organization costs, the $2.0 million upfront payment made to GenFleet pursuant to the collaboration and option agreement, and increased personnel costs, including non-cash stock compensation.

Selling, general & administrative expenses for the 2023 Period were $30.7 million, compared to $25.0 million for the 2022 Period. The increase of $5.7 million, or 22.8%, was primarily related to increased personnel costs, including non-cash stock compensation, additional costs in anticipation of a potential launch of avutometinib and defactinib in LGSOC, and increased consulting and professional fees.

Net loss for the 2023 Period was $87.4 million, or $3.96 per share (basic and diluted, each as adjusted for the Company’s reverse stock split), compared to $73.8 million, or $4.57 per share (basic and diluted, each as adjusted for the Company’s reverse stock split) for the 2022 Period.

For the 2023 Period, non-GAAP adjusted net loss was $85.2 million, or $3.86 per share (diluted, as adjusted for the Company’s reverse stock split), compared to non-GAAP adjusted net loss of $67.4 million, or $4.18 per share (diluted, as adjusted for the Company’s reverse stock split), for the 2022 Period. Please refer to the GAAP to non-GAAP Reconciliation attached to this press release.

Use of Non-GAAP Financial Measures

To supplement Verastem Oncology’s condensed consolidated financial statements, which are prepared and presented in accordance with generally accepted accounting principles in the United States (GAAP), the Company uses the following non-GAAP financial measures in this press release: non-GAAP adjusted net loss and non-GAAP net loss per share. These non-GAAP financial measures exclude certain amounts or expenses from the corresponding financial measures determined in accordance with GAAP. Management believes this non-GAAP information is useful for investors, taken in conjunction with the Company’s GAAP financial statements, because it provides greater transparency and period-over- period comparability with respect to the Company’s operating performance and can enhance investors’ ability to identify operating trends in the Company’s business. Management uses these measures, among other factors, to assess and analyze operational results and trends and to make financial and operational decisions. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of the Company’s operating results as reported under GAAP, not in isolation or as a substitute for, or superior to, financial information prepared and presented in accordance with GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. The determination of the amounts that are excluded from non-GAAP financial measures is a matter of management judgment and depends upon, among other factors, the nature of the underlying expense or income amounts. Reconciliations between these non-GAAP financial measures and the most comparable GAAP financial measures for the three months and year ended December 31, 2023 and 2022 are included in the tables accompanying this press release after the unaudited condensed consolidated financial statements.

About the Avutometinib and Defactinib Combination

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. In contrast to currently available MEK-only inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other MEK-only inhibitors. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, a selective FAK inhibitor, for the treatment of all patients with recurrent LGSOC regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC.

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS/MAPK driven tumors as part of its (Raf And Mek Program). RAMP 301 (NCT06072781) is a Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC. RAMP 201 (NCT04625270) is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and enrollment has been completed in each of the dose optimization and expansion phases and the low-dose evaluation.

Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) in combination with avutometinib and defactinib and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 (NCT05074810) and RAMP 204 (NCT05375994) trials, respectively. Supported by the "Therapeutic Accelerator Award" received from PanCAN, Verastem Oncology is conducting RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.

About GFH375 (VS-7375)

GFH375 (VS-7375) is a potential best-in-class, potent and selective oral KRAS G12D (ON/OFF) inhibitor, identified as the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. GenFleet plans to submit an IND in China for GFH375 (VS-7375) in the first half of 2024, and upon approval GenFleet is expected to initiate a Phase 1 trial in China in the second half of 2024. The collaboration includes three discovery programs, the first being the KRAS G12D inhibitor, and will provide Verastem Oncology with exclusive options to obtain licenses to each of the three compounds in the collaboration after successful completion of pre-determined milestones in Phase 1 trials. The licenses would give Verastem Oncology development and commercialization rights outside of the GenFleet territories of mainland China, Hong Kong, Macau, and Taiwan.

MOLECULAR PARTNERS REPORTS CORPORATE HIGHLIGHTS FROM Q4 2023 AND KEY FINANCIALS FOR FULL YEAR 2023

On March 14, 2024 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported its corporate highlights and audited financial results for the full year 2023 (Press release, Molecular Partners, MAR 14, 2024, View Source [SID1234641180]).

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"2023 was a year of successful innovation and execution on our strategy, focusing on novel mechanisms that we believe only DARPin therapies can deliver. The encouraging new clinical and preclinical data across our portfolio illustrate the versatility and differentiated promise of DARPin therapies and our long-term leadership in this field," said Patrick Amstutz, Ph.D. Molecular Partners’ Chief Executive Officer. "In 2024, we look forward to presenting further clinical data from our lead oncology program MP0533, and translating our significant progress across the Radio-DARPin Therapy and Switch-DARPin platforms into initiation of IND-enabling studies."

Research & Development

MP0533
In December 2023, the Company presented positive initial data from the first four dosing cohorts of its ongoing Phase 1/2a trial of MP0533 at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. Results from the first 11 patients treated with MP0533 indicated an acceptable safety profile as of the data cut-off across all four dosing regimens (DRs), with no dose-limiting toxicities observed. Two responders were observed at the time of presentation, including a patient achieving a complete response (CR) in DR 4 and another patient with morphological leukemia-free state (MLFS) in DR 3. These responses are particularly notable for having occurred at dose levels below those predicted as therapeutically active.

MP0533 is a novel tetra-specific T cell-engaging DARPin, which simultaneously targets the antigens CD33, CD123, and CD70 on AML cells as well as the immune activator CD3 on T cells. AML cells display higher co-expression at least two of these target antigens as compared with healthy cells. MP0533 binds with increasing avidity as the number of its target antigens present increases, dramatically favoring binding to AML cells over healthy cells. This unique avidity-driven mode of action is designed to enable T cell-mediated killing of AML cells while preserving a therapeutic window that minimizes damage to healthy cells.

The Phase 1/2a study is on track with dosing in DR 6 currently ongoing. The Company expects to present data from further cohorts receiving MP0533 in H1 2024. Based on current safety and tolerability data from the ongoing study, and based on discussion with treating investigators and key opinion leaders, a protocol amendment is being filed to expand enrollment to additional higher dose cohorts of MP0533 beyond the initially planned highest cohort (DR 7). The goal of the additional higher doses will be to explore the full potential efficacy of MP0533. The Company expects to enroll patients in the added higher cohorts seamlessly in H2 2024.

Switch-DARPin Platform
In 2023, the Company introduced the Switch-DARPin platform and presented data evidencing its mechanism-of-action. The Switch-DARPin platform represents a further evolution of the Company’s capabilities to deliver multispecific candidates to address different disease needs. The Switch-DARPin platform provides a logic-gated "on/off" function (the "Switch") to multispecific DARPin candidates leading to activation only in the presence of defined antigens. The objective is conditional activation of a targeted immune response.

In January 2024, the first program from the Switch-DARPin platform was introduced at the 42nd Annual J.P. Morgan Healthcare Conference, namely a cKIT x CD16a x CD47 multispecific Switch-DARPin candidate designed as next-generation targeted conditioning regimen for hematopoietic stem cell transplantation (HSCT) in AML and other diseases benefiting from HSCT such as genetic diseases. The cKIT x CD16a x CD47 Switch-DARPin program is designed to induce exhaustive killing of stem cells to increase long-term disease control post HSCT for AML patients, including those with a poor cytogenetic risk profile, and those currently not eligible for standard high-intensity conditioning. Our intent is to extend the access to potentially curative HSCT for more patients with AML and beyond.

The target-by-target rationale for this program’s design is:

cKIT is critical for stem cell maintenance and renewal and thus expressed on both hematopoietic and leukemic stem cells.
The CD16a DARPin engages NK cells and macrophages to selectively kill cKIT-positive cells.
The Switch-DARPin will block the CD47 "don’t eat me" signal only when the molecule binds on cKIT-positive cells, leveraging the power of CD47 inhibition without its associated toxicity to healthy cells.
The Company expects to present initial pre-clinical data from the first Switch-DARPin program cKIT x CD16a x CD47 in H1 2024 and to run preclinical proof-of-concept studies in H2 2024, which should provide strong translational efficacy data.

Radio-DARPin Therapy (RDT) Platform
In September 2023, Molecular Partners presented preclinical data from its RDT platform at the 36th Annual Meeting of the European Association of Nuclear Medicine (EANM) demonstrating a substantially increased tumor uptake of RDT candidates through an adjustment of systemic half-life, achieved by binding to the human serum albumin protein. These results expand on preclinical data that were previously reported at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting and Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting in 2023 and highlight that surface engineering of the DARPin backbone into a "Stealth" DARPin can lead to marked reduction of RDT candidate reabsorption by kidneys, addressing a key challenge for protein-based radionuclide delivery vectors. At the 42nd Annual J.P. Morgan Healthcare Conference in January 2024, Molecular Partners presented data showing the reduction of kidney absorption through novel engineered Stealth DARPins as well as enhanced tumor uptake via half-life engineering for several targets. Achieving improved tumor uptake and reduced kidney reabsorption has enabled the expansion of the RDT pipeline and strategy for the RDT portfolio.

Furthermore, in January 2024, Molecular Partners and Orano Med entered a strategic collaboration to co-develop 212Pb-based RDTs for patients with solid tumors. The deal combines the power of DARPins, as a highly differentiated modality for tumor-targeted delivery of radioisotopes, with Orano Med’s leading capabilities in Targeted Alpha Therapy and supply to further advance the RDT platform and expand Molecular Partners’ RDT portfolio.

The tumor-associated protein Delta-like ligand 3 (DLL3) was selected as the target of the Company’s lead RDT program to be advanced into IND-enabling studies in H1 2024. Expression of DLL3 is low in healthy tissue but significantly increased in certain tumor types, providing an opportunity for selective targeting through the high affinity and specificity offered by DARPins. The initiation of clinical studies and first-in-human data are expected in 2025 through co-development with Orano Med. Molecular Partners also expects to nominate additional targets and RDT candidates in 2024.

In addition to the above updates, Molecular Partners continued to progress its RDT portfolio of projects in partnership with Novartis.

MP0317
In November 2023, the Company presented additional positive dose-escalation data from its Phase 1 study of MP0317 in patients with advanced solid tumors at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). These data from 46 patients corroborated earlier reported findings of MP0317-induced CD40 activation and related remodeling of the tumor microenvironment (TME). At the time of the presentation, MP0317 monotherapy continued to display a favorable safety profile across all dosing cohorts up to the highest planned dose.

MP0317 enables tumor-localized immune activation through simultaneously targeting the immunostimulatory protein CD40 and fibroblast activation protein (FAP). FAP is expressed in high amounts around tumors. Through this proposed mechanism of action, MP0317 is designed to activate immune cells specifically within the tumor microenvironment, potentially delivering greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.

The Company expects to report the full dataset from the Phase 1 study dose-escalation in H1 2024.

Corporate Governance & Leadership Highlights

Dr. Philippe Legenne, M.D., MBA, MHS, assumed responsibilities as acting Chief Medical Officer in August 2023.

Dr. Legenne joined Molecular Partners in early 2020. Over this time, he has led the clinical development strategy and execution across the Molecular Partners portfolio. Prior to joining Molecular Partners, Philippe held positions of increasing responsibility at JNJ, GSK, and Novartis, both in the United States and Europe. In his most recent role prior to Molecular Partners, Philippe led the EU medical organization for the oncology portfolio at Amgen. He received his medical degree from the Université de Lille (France), an MBA from ESSEC Business School (Paris) and a Master’s degree in health economics from Université Paris Dauphine-PSL.​

Update to Class Action Lawsuit

On February 29, 2024 a putative class action complaint against the Company, its directors, and certain of its executive officers was dismissed in the Company’s favor, and the case has been ordered closed. The original case was filed on July 12, 2022 in the U.S. District Court for the Southern District of New York.

2023 Financial Highlights

In the financial year 2023, Molecular Partners recognized total revenues and other income of CHF 7.0 million (2022: CHF 189.6 million) and incurred total expenses of CHF 68.1 million (2022: CHF 73.0 million). This led to an operating loss of CHF 61.1 million for 2023 (2022: Operating profit of CHF 116.6 million). The net financial loss recorded in 2023 was CHF 0.9 million, compared to a net financial gain of CHF 1.2 million in 2022. This resulted in a 2023 net loss of CHF 62.0 million (2022: Net profit of CHF 117.8 million).

The net cash used in operating activities in 2023 was CHF 59.0 million (2022: Net cash from operating activities CHF 118.6 million). Including short-term time deposits, the cash and cash equivalents position decreased by CHF 62.2 million as compared to year-end 2022, to CHF 186.9 million as of December 31, 2023 (December 31, 2022: CHF 249.1 million). Total shareholders’ equity stood at CHF 176.4 million as of December 31, 2023, a decrease of CHF 58.8 million (December 31, 2022: CHF 235.2 million).

The Company’s cash position and short-term time deposits were CHF 186.9 million as per December 31, 2023, and continue to provide the Company with financial flexibility and a forecasted cash runway well into 2026.

The Company’s balance sheet remained debt-free in 2023. As of December 31, 2023, the Company employed 167.5 FTE (full-time equivalents), down 4% year-on-year. About 83% of the employees are employed in R&D-related functions.

Key figures as of December 31, 2023

Key Financials (CHF million, except per share, FTE data) FY 2023 FY 2022 Change
Total revenues and other income 7.0 189.6 (182.6 )
R&D expenses (48.7 ) (50.7 ) 2.0
SG&A expenses (19.4 ) (22.3 ) 2.9
Operating result (68.1 ) (73.0 ) 4.9
Net finance result (61.1 ) 116.6 (177.7 )
Net result (0.9 ) 1.2 (2.1 )
Basic net result per share (in CHF) (1.89 ) 3.63 (5.52 )
Diluted net result per share (in CHF) (1.89 ) 3.54 (5.43 )
Net cash (used in) from operating activities (59.0 ) 118.6 (177.6 )
Cash & cash equivalents (incl. short-term time deposits) 186.9 249.1 (62.2 )
Total shareholders’ equity 176.4 235.2 (58.8 )
Number of total FTE 167.5 175.3 -7.8

Financial outlook 2024
For the full year 2024, at constant exchange rates, the Company expects total operating expenses of CHF 70-80 million, of which around CHF 8 million will be non-cash effective costs for share-based payments, IFRS pension accounting and depreciation.

Documentation

This press release, the Company’s Annual Report on Form 20-F for the year ended December 31, 2023 to be filed with the U.S. Securities and Exchange Commission (SEC), and the Company’s annual report 2023 will be made available through www.molecularpartners.com under the investor section after 9.00 pm CET (4.00 pm EST) on March 14, 2024.

Full Year 2023 Conference Call & Audio Webcast

Molecular Partners will hold a conference call and audio webcast on March 15, 1.00 pm CET (8.00 am EST).
To register for the full year 2023 conference call, please dial the following numbers approximately 10 minutes before the start of the presentation:

Participant Dial In (Toll Free): 1-866-652-5200
Participant International Dial In: 1-412-317-6060
Switzerland Toll Free: 0800-246787

Participants in the conference call will have the opportunity to ask questions after the presentation.

Audio webcast

The full year 2023 results will be webcast live and will be made available on the Company’s website under the investor section. The replay will be available for 90 days following the presentation.

Autolus Therapeutics Reports Full Year 2023 Financial Results and Business Updates

On March 14, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported its operational and financial results for the full year ended December 31, 2023 (Press release, Autolus, MAR 14, 2024, View Source [SID1234641179]).

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"We’re delighted to be starting 2024 in such a strong financial position; our recently announced strategic alliance with BioNTech, coupled with two equity financing transactions, raised gross proceeds of $600 million. Combined with our 2023 ending cash of $240 million, this enables us to drive the full launch and commercialization of obe-cel in r/r adult ALL and establish Autolus as a potential leader in the delivery of CAR T therapy to patients with autoimmune diseases," said Dr. Christian Itin, Chief Executive Officer of Autolus.

"2023 was a transformational year for the Company. Our lead program, obe-cel, demonstrated strong data in B-ALL in the pivotal FELIX study, we fully validated our commercial manufacturing facility, The Nucleus, to support our regulatory submissions and we submitted our first BLA for obe-cel to the United States Food and Drug Administration (FDA) in November, with a PDUFA target action date of November 16, 2024. We also just submitted an MAA to the European Medicines Agency (EMA).

"Beyond B-ALL, we see a significant opportunity for obe-cel in autoimmune disease. Our Phase 1 dose confirmation trial in refractory SLE is now open for enrollment. We believe obe-cel’s clinical profile, together with our commercial product delivery base and infrastructure, will help to drive an accelerated and differentiated expansion in autoimmune diseases and we look forward to sharing initial data from the study in late 2024.

"For now, we remain fully focused on preparing for a potential obe-cel launch and successfully transitioning Autolus to a commercial stage company. Pre-commercial and product delivery activities are well underway, and we are on track to make obe-cel available to B-ALL patients as soon as possible, following a potential approval."

Key obecabtagene autoleucel (obe-cel) updates and anticipated milestones:

Obe-cel in relapsed / refractory (r/r) adult ALL – The FELIX Study
Obe-cel BLA for r/r B-ALL submitted to the FDA in November 2023; PDUFA target action date of November 16, 2024. A marketing authorization application (MAA) to the European Medicines Agency (EMA) was just submitted and an MAA submission to the MHRA in the UK is planned for the second half of 2024.
Pooled analysis of the FELIX Phase 1b/2 study presented at ASH (Free ASH Whitepaper) in December 2023 demonstrated prolonged event free survival and low overall immunotoxicity across all cohorts in r/r B-ALL, and particularly in patients with low leukemic burden at lymphodepletion. Additionally, data from a pooled analysis from the ALLCAR19 study and FELIX Phase 1b in r/r B-ALL showed durable remissions with obe-cel as a stand-alone therapy in a subset of patients after a median follow up of >3 years. Further long-term data from the FELIX study is anticipated at medical conferences in 2024.

Obe-cel in B-cell mediated autoimmune diseases
The Phase 1 dose confirmation study in refractory systemic lupus erythematosus (SLE) patients has the first site open for enrollment; initial clinical data expected in late 2024.
Pipeline clinical trials, in collaboration with University College London (UCL), updates and anticipated milestones:

AUTO8 in Multiple Myeloma – Phase 1 MCARTY Study
AUTO8 is a next-generation product candidate for multiple myeloma, which includes two CARs for the multiple myeloma targets, BCMA and CD19. Initial data from the MCARTY Phase 1 study in multiple myeloma presented at ASH (Free ASH Whitepaper) in December 2023 showed AUTO8 was well tolerated, with responses observed in all patients. Further updates from the MCARTY study are anticipated during 2024.
AUTO6NG in Neuroblastoma – Phase 1 MAGNETO Study
AUTO6NG contains a CAR that targets GD2 alongside additional programming modules to enhance the activity and persistence. A Phase 1 clinical study in children with r/r neuroblastoma was opened for enrollment in the fourth quarter of 2023.
Post-period:

Strategic developments:

Strategic alliance with BioNTech SE

In February 2024, BioNTech and Autolus announced a strategic CAR T cell therapy collaboration to advance their pipelines and expand late-stage programs, for $50 million cash upfront and up to $582 million in potential option exercise and milestone payments. Additionally, Autolus sold $200 million of ADSs to BioNTech in a concurrent private placement financing transaction.

Overview:

BioNTech has right to utilize Autolus’ manufacturing capacity, know-how and cost-efficiencies to accelerate the planned clinical development and commercialization of BNT211
BioNTech to support launch and expansion of development program of Autolus’ lead cell therapy candidate obe-cel and will receive a royalty on net sales
BioNTech has co-commercialization options for Autolus’ AUTO1/22 and AUTO6NG programs, and an option to access a suite of Autolus target binders and cell programming technologies
Underwritten offering

In February 2024, Autolus completed an underwritten registered direct offering in the United States at a price of $6.00 per ADS, for total gross proceeds of $350 million.

Recent Operational Updates:

In March 2024, following the most recent GMP inspection by the MHRA in February 2024, The Nucleus manufacturing facility in Stevenage obtained a Manufacturer’s Importation Authorization (MIA), together with the accompanying GMP certificate. This authorization enables Autolus to manufacture products for global commercial and clinical supply at The Nucleus, effective as of March 18, 2024.
In February 2024, Autolus promoted Dr. Chris Williams to Chief Business Officer and Alex Driggs to Senior Vice President, Legal Affairs and General Counsel. Chris has been with the Company since its inception, having negotiated on behalf of UCL the spin off and formation of Autolus. Alex has been with Autolus since 2018 in the role of General Counsel.
Dr. Edgar Braendle has notified the Company that he will step down as Chief Development Officer to pursue other opportunities. Edgar will continue to advise the company during the BLA and MAA review process. Miranda Neville, SVP and obe-cel Program Leader will run the Development team.
Autolus announced the appointment of Elisabeth (Lis) Leiderman, M.D. and Robert W. Azelby to its Board of Directors. Dr. Leiderman brings extensive transactional and financial expertise, and Mr. Azelby brings more than 30 years of biopharmaceutical leadership and commercial experience to Autolus’ Board.
Scientific Publications:

In January 2024, Autolus announced the publication of a paper in ACS Chemical Biology entitled: ‘Designer small molecule control system based on Minocycline induced disruption of protein-protein interaction’ – Jha et al., ACS Chemical Biology (2024) doi:10.1021/acschembio.3c00521; [Link]
In February 2024, Autolus announced the publication of a paper in Nature Communications entitled: ‘Structure-Guided Engineering of Immunotherapies Targeting TRBC1 and TRBC2 in T Cell Malignancies’ – Ferrari et al., Nat Commun 15, 1583 (2024) doi:10.1038/s41467-024-45854-3; [Link]
In March 2024, Autolus announced the publication of a paper in Blood Cancer Journal entitled: ‘Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry – Horna et al., Blood Cancer J. 14, 34 (2024) doi: 10.1038/s41408-024-01002-0; [Link]

2024 Expected News Flow:

Obe-cel FELIX data update at ASCO (Free ASCO Whitepaper), EHA (Free EHA Whitepaper) & ASH (Free ASH Whitepaper) June & Dec 2024
Obe-cel Marketing Authorization Application to MHRA Second half 2024
Obe-cel U.S. FDA PDUFA target action date November 16, 2024
Obe-cel in autoimmune disease – initial data from SLE Phase 1 study Late 2024

Financial Results (Unaudited) for the Full Year Ended December 31, 2023

Cash and cash equivalents at December 31, 2023 totaled $239.6 million, as compared to $382.4 million at December 31, 2023.

Total operating expenses, net for the year ended December 31, 2023, were $179.7 million, as compared to $143.4 million, for the year ended December 31, 2022.

Research and development expenses increased from $117.4 million to $130.5 million for the year ended December 31, 2023, compared to the same period in 2022. This change was primarily due to increases in operating costs related to the Company’s new commercial manufacturing facility, contractual milestone payments and employee salaries and related costs, a decrease in our U.K. reimbursable R&D tax credits claimable through the U.K. small and medium-sized entity (SME) scheme and partially offset by decreases in clinical and manufacturing costs related to the Company’s obe-cel clinical product candidate.

In prior years, Autolus reported the R&D tax credits as income tax benefit on its statements of operations. The Company has revised its financial presentation, including the prior years, and will now present such tax credits as a reduction in research and development expense. As a result, income tax benefit has reduced by $19.5 million and $24.6 million for the years ended December 31, 2023, and 2022, respectively, with corresponding reductions in research and development expenses and total operating expenses.

General and administrative expenses increased from $31.9 million to $46.7 million for the year ended December 31, 2023, compared to the same period in 2022. This increase was primarily due to salaries and other employment-related costs driven by an increase in general and administrative headcount supporting the overall growth of the business, primarily relating to pre-commercialization activities.

Net loss attributable to ordinary shareholders was $208.4 million for the year ended December 31, 2023, compared to $148.8 million for the same period in 2022. The basic and diluted net loss per ordinary share for the year ended December 31, 2023, totaled $(1.20), compared to a basic and diluted net loss per ordinary share of $(1.57) for 2022.

Autolus estimates that, with its current cash and cash equivalents and proceeds received from the strategic alliance with BioNTech and the private placement and underwritten equity financing, it is well capitalized to drive the full launch and commercialization of obe-cel in r/r adult ALL as well as to advance its pipeline development plans, which includes providing runway to data in the first pivotal study of obe-cel in autoimmune disease.

Anocca AB Licenses Gene Editing Technology from EmendoBio Inc.

On March 14, 2024 Anocca AB (Anocca), a leading T cell receptor-engineered T cell (TCR-T) cellular therapeutics company, and EmendoBio Inc. (EmendoBio), a nuclease discovery and gene editing therapeutics company, reported a non-exclusive licensing agreement for the use of EmendoBio’s novel OMNI-A4 nuclease to accelerate the manufacture and development of Anocca’s deep pipeline of TCR-T cell therapies for difficult-to-treat solid cancers (Press release, Anocca, MAR 14, 2024, View Source [SID1234641178]).

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"Integrating EmendoBio’s nuclease into our manufacturing process supports Anocca’s aim of generating the highest-quality cell therapy products. This next-generation gene editing system provides the precision and efficiency needed to scale out production of our growing libraries of TCR-T products in a high-precision manufacturing process. We are excited to work with EmendoBio to develop gene-edited TCR-T cell therapies as we prepare for our first clinical program targeting the KRAS driver mutation in a hard-to-treat solid cancer" said Anocca’s CEO and co-founder, Reagan Jarvis.

"This non-exclusive licensing agreement marks a significant milestone in the field of T cell therapy," said Dr. Ei Yamada, Director of EmendoBio. "Together with Anocca, we are embracing the shared vision of harnessing the potential of gene editing and cellular therapies to make a profound impact on patient outcomes. Our combined expertise will unlock novel avenues for therapeutic development and push the boundaries of what’s possible in advanced medicine."

Anocca recently received certification of GMP compliance and a manufacturing license from the Swedish regulators for their cell therapy production facility, the largest in the Nordics. EmendoBio’s technology strengthens Anocca’s manufacturing capability and provides a foundation for the ambitious goal of reaching more patients faster with personalised treatments targeting the underlying genetic drivers of hard-to-treat cancers. The licensed gene editing technology is part of EmendoBio’s portfolio of proprietary nucleases developed to be highly active and specific for cell therapy applications.

Anocca’s and Emendo’s commitment to innovation and scientific excellence sets the stage for a promising future in T cell therapies. The agreement not only underscores the significance of collaborative efforts in the biotechnology sector but also reinforces both companies’ dedication to improving global healthcare outcomes.

Cellipont Bioservices and Wugen Sign Agreement for the Clinical Manufacture of Wugen’s Off-the-shelf CAR-T Cellular Therapies

On March 14, 2024 Cellipont Bioservices, a leading cell therapy Contract Development and Manufacturing Organization (CDMO), and Wugen, Inc., a clinical-stage biotechnology company developing allogeneic, off-the-shelf cell therapies to treat a broad range of hematological and solid tumor malignancies, reported the signing of an agreement for the manufacturing of their CAR-T cell therapies (Press release, Wugen, MAR 14, 2024, View Source [SID1234641174]).

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Under the agreement, Cellipont Bioservices will be providing the technology transfer and production of Wugen’s allogeneic CAR-T cell therapies at their new purpose-built 76,000 sq. ft. manufacturing facility.

Wugen is developing the next generation of off-the-shelf memory natural killer (NK) and CAR-T cell therapies for cancer. The company’s investigational cell therapies originate from healthy donors and are further engineered to enhance their function of eliminating cancer cells. Their NK cell and CAR-T immuno-oncology therapies address the needs of patients with solid tumors, acute myeloid leukemia (AML) and T-cell malignancies.

"We are excited to collaborate with Cellipont Bioservices, leveraging their expertise in cell therapy manufacturing to carry out our mission of bringing innovative CAR-T cell therapies to patients in need. This new partnership helps enable Wugen to achieve our mission to help patients with hematological malignancies with off-the-shelf cell therapies," said Kumar Srinivasan, Ph.D., MBA, president and CEO of Wugen.

"We are thrilled to partner with Wugen, Inc. in advancing their groundbreaking CAR-T cell therapies. This collaboration underscores our commitment to driving innovation and accelerating the development of life-saving treatments for patients worldwide," said Edwin Beale, CCO of Cellipont.