On November 8, 2024 Medigene AG (Medigene or the "Company", FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, reported recent advances in its proprietary End-to-End Platform to create optimal safe, sensitive, and specific (3S) T cell receptors that can be applied in various modalities, including therapies utilizing T cell receptor engineered T (TCR-T) cells, TCR-guided T cell engagers (TCR-TCEs) and TCR-natural killer cell therapies (TCR-NK) at the Cell 2024 Conference by Oxford Global taking place in London, UK from November 6-8, 2024 (Press release, MediGene, NOV 8, 2024, View Source [SID1234648038]).

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Data presented and discussed included

Kirsty Crame, MD, participated in the panel "Exploring Autologous vs. Allogeneic Therapies." which covered clinical insights, patient considerations, key immunological factors, and manufacturing challenges associated with each therapeutic approach.
Kirsty Crame, MD, held the keynote address "Making the Ordinary Extraordinary: MDG1015 A Clinic Ready 3rd Generation TCR-T Therapy" providing a comprehensive overview of MDG1015. MDG1015 is a first-in-class, 3rd generation T cell receptor engineered T cell (TCR-T) therapy targeting NY-ESO-1 / LAGE-1a, a well-recognized and validated cancer-testis antigen, which is expressed in multiple tumor types. MDG1015 received IND approval in Q3 2024 and is on track for CTA filing in Q4 2024.
Prof. Dolores Schendel presented the "TCR-T Platform for Solid Tumors" covering Medigene’s End-to-End Platform offering advanced technologies for developing 3S TCRs that can be utilized across multiple modalities. Precision tools enabling selection of 3S TCRs with high specificity, sensitivity, and safety for accurate tumor targeting were presented. Additionally, armoring and enhancement technologies were showcased which empower TCR-T cells to perform optimally within the challenging microenvironments of solid tumors. Furthermore, innovative tagging and tracing tools were highlighted, enabling seamless tracking of 3S TCRs throughout all phases of research and clinical development.
The presentations will be available on Medigene’s website: View Source

"Among other factors, the success of TCR-guided therapies for solid tumors hinges on several key innovations: developing optimal TCRs that are safe, sensitive, and specific; enhancing engineered cells to overcome the tumor microenvironment; and refining manufacturing strategies for optimized drug composition and timely patient delivery," said Dolores Schendel, Medigene’s Chief Scientific Officer. "Our E2E Platform addresses each of these critical areas, positioning us to deliver optimal 3S TCRs that can be utilized in multiple therapeutic modalities, such as TCR-T therapies, TCR-TCEs and TCR-NK cell therapies. This approach of developing different TCR-guided therapies enables us to provide innovative treatment options tailored to patients across various indications, disease stages, and specific individual needs."

On November 8, 2024 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, reported initial preclinical data for FT836, a multiplexed-engineered, chimeric antigen receptor (CAR) T-cell product candidate targeting major histocompatibility complex (MHC) proteins A (MICA) and B (MICB) at the 2024 Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting being held in Houston, TX on November 6-10, 2024 (Press release, Fate Therapeutics, NOV 8, 2024, View Source [SID1234648037]). The expression of MICA/B cell-surface proteins is induced by cellular stress or malignant transformation, and is detectable across many types of cancer cells with limited expression on healthy tissue. FT836 incorporates multiple next-generation synthetic controls of CAR T-cell function including the Company’s novel Sword & Shield technology, which is comprised of a constellation of genetic edits that both target and evade host alloreactive immune cells and is designed to promote functional persistence of off-the-shelf CAR T-cell therapies without conditioning chemotherapy.

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"The novel suite of synthetic controls incorporated into FT836 is intended to address critical challenges that have limited CAR T-cell safety and efficacy in treating solid tumors including on-target, off-tumor toxicity, effector cell suppression in the tumor microenvironment, tumor heterogeneity, and limited functional persistence," said Bob Valamehr, Ph.D., President of Research & Development of Fate Therapeutics. "Our FT836 preclinical data presented today at SITC (Free SITC Whitepaper) support the pan-cancer activity of MICA/B targeting, and indicate that our next-generation, iPSC-derived CAR T-cell platform has the potential to drive potent and durable anti-tumor activity without the need for administration of conditioning chemotherapy to deplete host immune cells."

Preclinical Data

MICA/B targeting is emerging as a novel cancer-specific strategy to attack a wide range of solid tumors, however, proteolytic cleavage and shedding of MICA/B at the membrane-proximal α3 domain is a common mechanism of cancer resistance and escape from canonical NKG2D-mediated recognition. FT836 is designed to uniquely target and bind the α3 domain, which has been shown to stabilize MICA/B expression and induce robust cytolytic killing of tumor cells. At an oral presentation today at SITC (Free SITC Whitepaper) entitled "Development of an Off-the-Shelf, MICA/B Targeting CAR T Cell to Overcome Pan-tumor Escape Mechanism for Solid Tumors", scientists from the Company highlighted that FT836 exerted potent and durable anti-tumor activity in vivo across a broad array of solid tumors. In addition, treatment of tumor cells with chemotherapy or radiation therapy in vitro elicited an increase in MICA/B expression and further enhanced the cytolytic activity of FT836, indicating the potential for combination with standard-of-care regimens used for the treatment of solid tumors.

Novel Sword & Shield Technology

FT836 is also the Company’s first product candidate to incorporate its novel Sword & Shield technology, which utilizes a 4-1BB-targeted CAR (ADR) alongside the complete knock-out of CD58 (CD58KO), to both target and evade host alloreactive immune cells. In preclinical studies presented at SITC (Free SITC Whitepaper), iPSC-derived Sword & Shield CAR T cells demonstrated functional persistence and durable anti-tumor activity in vivo that was uniquely maintained upon supraphysiological challenge with alloreactive T cells, indicating the potential of Sword & Shield CAR T cells to thrive without administration of conditioning chemotherapy to deplete host immune cells. The Company’s novel Sword & Shield technology was also featured in a poster presentation at SITC (Free SITC Whitepaper) entitled "Alloimmune Defense Receptor Combined with Genetic Ablation of Adhesion Ligand CD58 is a Comprehensive Approach to Promote Functional Persistence of Allogeneic Cell Therapies without Conditioning Chemotherapy".

On November 8, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), an early-commercial stage biopharmaceutical company developing next-generation programmed T cell therapies, reported that the U.S. Food and Drug Administration (FDA) has granted marketing approval for AUCATZYL (obecabtagene autoleucel) for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r B-ALL) (Press release, Autolus, NOV 8, 2024, View Source [SID1234648036]).

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"Adult ALL is an extremely aggressive cancer, and there is a high unmet medical need that exists in the treatment of patients with this disease once they relapse, where historically they suffer from poor outcomes," said Elias Jabbour, MD, U.S. lead investigator of the FELIX study and professor of Leukemia, ALL Section Chief, at The University of Texas MD Anderson Cancer Center, Houston, Texas. "This milestone approval, based on the demonstrated clinical benefit of AUCATZYL, brings new hope for adult patients with relapsed/refractory B-ALL."

AUCATZYL was approved by the FDA based on results from the FELIX clinical trial of obe-cel in adult patients with r/r B-ALL. In the morphological disease cohort, 94 patients received at least one infusion of AUCATZYL of which 65 patients had > 5% blasts in the bone marrow after screening and prior to the start of lymphodepletion therapy and received a conforming product, qualifying them as efficacy evaluable. In the efficacy evaluable patients (n=65), 63% achieved overall complete remission (OCR1) which includes 51% of patients with CR at any time and 12% patients with CRi at any time. The major efficacy outcome was complete remission within 3 months, which was achieved in 42% patients, and the median duration of remission (DOR) was 14.1 months. AUCATZYL showed low levels of Cytokine Release Syndrome (CRS), with 3% Grade 3 events, and no Grade 4 or 5 events. Grade ≥ 3 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) was reported in 7% of patients. No REMS was required by the FDA for AUCATZYL.

The safety of AUCATZYL includes a boxed warning for CRS, neurologic toxicities, and secondary hematological malignancies. ICANS, including fatal or life-threatening reactions, occurred in patients receiving AUCATZYL. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies. In the FELIX trial, the most common non-laboratory adverse reactions (incidence ≥ 20%) included CRS, infections-pathogen unspecified, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, ICANS, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage.

"Based on the experience in the FELIX trial AUCATZYL is highly active and can be well managed, offering an attractive risk benefit profile for B-ALL patients," said Dr. Claire Roddie, MD, PhD, FRCPath, Lead investigator of the FELIX study and Associate Professor of Haematology at the University College London (UCL) Cancer Institute. "In the FELIX trial AUCATZYL has shown long term persistence and deep responses which we believe are critical for long term remissions in B-ALL."

"We are so pleased to now be able to offer AUCATZYL, our first commercial product, to adult r/r B-ALL patients in the U.S. This approval would not have been possible without the support of all the patients, their families and caregivers, their treating physicians and the nurses and investigators at the treatment centers – thank you," said Dr. Christian Itin, Chief Executive Officer of Autolus. "This milestone is the culmination of many years of hard work, the foundational work by our partners at UCL and the unwavering commitment of our internal team, our external partners and shareholders. This is a proud day for Autolus."

AUCATZYL will be manufactured at Autolus’ dedicated commercial manufacturing site, the Nucleus, in Stevenage, UK. The site was granted a Manufacturer’s Importation Authorization (MIA) and a GMP certificate from the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) in March 2024, and was inspected as part of the FDA approval process. No major or critical observations were identified by either the MHRA or FDA during the site inspections. The Nucleus will supply AUCATZYL globally, with Cardinal Health serving as Autolus’ commercial distribution partner in the U.S. Autolus will now engage with existing treatment centers to complete the onboarding process and initiate the first scheduling of patients to make AUCATZYL commercially available in the U.S.

ALL is an aggressive type of blood cancer that can also involve the lymph nodes, spleen, liver, central nervous system and other organs. Approximately 8,400 new cases of adult ALL are diagnosed every year in the US and EU, with around 3,000 patients in the relapsed refractory setting.1 Survival rates remain very poor in adult patients with r/r ALL, with median overall survival of eight months.2 In frontline treatment for adult r/r B-ALL, up to 50% of patients will ultimately relapse, and the standard-of-care treatment can trigger severe toxicities and may be burdensome for some patients.3,4

Marketing authorisation applications (MAAs) for obe-cel in adult r/r ALL are being reviewed by the regulators in both the EU and the UK, with a submission to the European Medicines Agency (EMA) accepted in March 2024, and a submission accepted by the UK MHRA in August 2024.

Conference Call

Management will host a conference call and webcast on November 11 at 8:30 am EST/1:30 pm BST to discuss the AUCATZYL approval. Conference call participants should pre-register using this link to receive the dial-in numbers and a personal PIN, which are required to access the conference call.

A simultaneous audio webcast and replay will be accessible on the events section of Autolus’ website.

On November 8, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) reported that its executives will be speaking at the following investor conferences (Press release, Gilead Sciences, NOV 8, 2024, View Source [SID1234648035]):

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Jefferies London Healthcare Conference on Wednesday, November 20 at 9:30 AM Greenwich Mean Time
Piper Sandler Annual Healthcare Conference on Tuesday, December 3 at 11:00 AM Eastern Time
Annual Evercore ISI HealthCONx Conference on Wednesday, December 4 at 11:40 AM Eastern Time

The live webcasts can be accessed at the company’s investors page at investors.gilead.com. The replays will be available for at least 30 days following the presentation.

On November 8, 2024 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel radioimmunotherapy and antibody-based therapeutic products for the treatment of cancer, reported financial results for the third quarter ended September 30, 2024 (Press release, Y-mAbs Therapeutics, NOV 8, 2024, View Source [SID1234648034]).

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"The third quarter of this year was one of continued focus and execution across our DANYELZA commercial business and our novel SADA PRIT radiopharmaceutical platform development pipeline," said Michael Rossi, President and Chief Executive Officer. "Physician usage of DANYELZA in the U.S. continues to remain very strong for patients with relapsed/refractory high-risk neuroblastoma. In addition, we continue to drive ex-U.S. market expansion with our new exclusive license and distribution agreement with Nobelpharma in Japan and the launch of our named patient program in Turkey. From a SADA PRIT pipeline standpoint, we expect to complete Part A of our GD2-SADA Phase 1 trial this year and present that data in the first quarter of next year."

Third Quarter 2024 and Recent Corporate Highlights

● Effective October 29, 2024, Y-mAbs entered into an exclusive license and distribution agreement with Nobelpharma for the development and commercialization of DANYELZA in Japan. Pursuant to the agreement, the Company recognized an upfront payment of $2.0 million in the fourth quarter of 2024. Y-mAbs is entitled to receive up to $31.0 million in product and commercial milestone payments in addition to profit sharing on the commercial sales of DANYELZA, if successfully approved and commercialized in Japan.
● Y-mAbs received notification of the accepted patent extension for DANYELZA, US 9,315,585, through February 2034.
● The Company’s named patient program for DANYELZA launched in Turkey with partner TRPharm İlaç Sanayi Ticaret A.Ş. and TRPharm FZ-LLC.
● Y-mAbs presented new clinical and preclinical data from studies evaluating anti-GD2 therapy naxitamab and the Company’s first program from its Self-Assembly DisAssembly Radioimmunotherapy Technology Platform ("SADA PRIT"), GD2-SADA, respectively, in neuroblastoma in poster presentations at the American Academy of Cancer Research Special Conference in the Advanced in Pediatric Cancer Research on September 6-7, 2024 in Toronto, Canada.
● The Company entered into a lease agreement for a term of ten years and nine months for office space in Princeton, New Jersey, where the Company plans to transition its headquarters in the first half of 2025 upon being provided access to the location.

Graphic

Financial Results

Revenues

Total net revenues for the quarter ended September 30, 2024 were $18.5 million, a 10% decline over total net revenues for the quarter ended September 30, 2023 of $20.5 million, which included $0.5 million in license revenue, primarily driven by decreased net product revenues in both U.S. and ex-U.S. markets.

Total net revenues for the nine months ended September 30, 2024 were relatively flat compared to the nine months ended September 30, 2023, at $61.2 million and $61.5 million, respectively. The slight decrease was driven by a $0.7 million decrease in ex-U.S. DANYELZA net product revenues in the nine months ended September 30, 2024, which was partially offset by increased net product revenues in the U.S.

The Company’s U.S. DANYELZA net product revenues were $15.3 million and $16.1 million for the three months ended September 30, 2024 and 2023, respectively, representing a 5% decline, primarily due to an unfavorable price mix, partially offset by increased volume of 5% vial growth over the same time period.

Y-mAbs’ ex-U.S. DANYELZA net product revenues for the quarter ended September 30, 2024 were $3.1 million, a 19% decline from $3.9 million in the comparable period in 2023, primarily driven by decreased volume from Western Europe partially offset by volume increases in the remaining ex-U.S. territories.

As of September 30, 2024, Y-mAbs had delivered DANYELZA to 68 centers across the U.S. since initial launch, with three new accounts added in the U.S. in the third quarter of 2024. During the quarter ended September 30, 2024, approximately 65% of the vials sold in the U.S. were sold outside of Memorial Sloan Kettering Cancer Center ("MSK"), compared to 67% in the second quarter ended June 30, 2024.

The Company did not have license revenue for the quarter ended September 30, 2024. The Company had license revenues of $0.5 million for the nine months ended September 30, 2024, from its Latin America distribution partner, Adium, related to price approval for DANYELZA in Brazil from the Brazilian Medicines Market Regulation Chamber. The Company had license revenues of $0.5 million for the quarter and nine months ended September 30, 2023 from Adium, recognized upon the September 2023 achievement of marketing authorization for DANYELZA in Mexico.

Operating Costs and Expenses

Cost of Goods Sold

Cost of goods sold were $2.3 million and $2.6 million for the quarter ended September 30, 2024 and 2023, respectively. Cost of goods sold were $7.4 million and $9.3 million for the nine months ended September 30, 2024 and 2023, respectively. Cost of goods sold included lower vial volumes of 1% and 37% in the three and nine months ended September 30, 2024, compared to the same periods in 2023, respectively. Cost of goods sold also included $0.4 million and $0.8 million inventory write-downs in the three and nine months ended September 30, 2023, respectively.

The Company defines gross margin as net product revenues less cost of goods sold divided by net product revenues. The Company’s gross margins was relatively unchanged in the quarter ended September 30, 2024, compared to the comparable periods in 2023. The Company’s gross margins increased in the nine months ended September 30, 2024, compared to the comparable period in 2023, due to a favorable gross profit mix from revenue in international regions, particularly Eastern Asia that had an inventory stocking order in the nine months ended September 30, 2024, and inventory write-downs during the comparable periods in 2023, as noted above.

Research and Development

Research and development expenses were $11.2 million for the quarter ended September 30, 2024, a decrease of $4.2 million when compared with the same period in 2023. The decrease in research and development expenses was primarily attributable to the recognition of $4.1 million of milestone and license acquisition costs related to the Company’s SADA license agreement during the three months ended September 30, 2023, as certain time-based clinical milestones within the agreement were determined to be probable based on the availability of necessary data and the assessment of clinical progress in the third quarter of 2023.

For the nine months ended September 30, 2024, research and development expenses were $36.8 million, a decrease of $4.0 million when compared with the same period in 2023. The decrease in the research and development expenses was primarily attributable to recognition of $4.1 million of milestone and license acquisition costs related to the Company’s SADA license agreement during the nine months ended September 30, 2023, as noted above.

Selling, General, and Administrative

Selling, general, and administrative expenses were $13.6 million and $10.2 million for the quarters ended September 30, 2024 and 2023, respectively. The $3.4 million increase in the selling, general and administrative expenses was primarily attributable to a $1.2 million increase related to the Company’s former Chief Financial Officer’s separation and consulting agreements, $1.1 million increase in personnel cost, inclusive of stock-based compensation and $0.5 million in professional and consulting fees.

For the nine months ended September 30, 2024, selling, general, and administrative expenses were $42.3 million, an increase of $8.5 million compared with the same period in 2023. The increase was primarily attributable to a net impact of $3.6 million related to the settlement of a shareholder class-action lawsuit in the nine months ended September 30, 2024, and an additional legal settlement of $0.2 million in the nine months ended September 30, 2024. The increase also includes a $1.2 million increase related to our former Chief Financial Officer’s separation and consulting agreements, $1.1 million increase in personnel cost inclusive of stock-based compensation and $0.8 million in professional and consulting fees.

Interest and Other Income

Interest and other income were $1.9 million for the quarter ended September 30, 2024, as compared to $0.2 million for the quarter ended September 30, 2023. The increase of $1.7 million was primarily due to a $1.9 million of foreign currency transactional gains in the three months ended September 30, 2024, partially offset by a $0.2 million decrease in interest earned on the Company’s cash and cash equivalents.

For the nine months ended September 30, 2024 and 2023, the interest and other income was $3.0 and $2.4 million, respectively. The increase of $0.6 million was primarily due to $1.1 million of foreign currency transactional gains, partially offset by a $0.3 million decrease in interest earned on the Company’s cash and cash equivalents.

Net Loss

Y-mAbs reported a net loss for the quarter ended September 30, 2024, of $7.0 million, or ($0.16) per basic and diluted share, compared to a net loss of $7.7 million, or ($0.18) per basic and diluted share, for the quarter ended September 30, 2023. The decrease in net loss for the quarter ended September 30, 2024 was primarily driven by decreased operating expenses and foreign currency transactional gains, partially offset by decreased net product revenue.

For the nine months ended September 30, 2024, the Company reported a net loss of $22.9 million, or ($0.52) per basic and diluted share, as compared to net loss of $20.4 million, or ($0.47) per basic and diluted share, for the nine months ended September 30, 2023. The increase in net loss for the nine months ended September 30, 2024 was primarily driven by the net $3.8 million in charges related to the Company’s two legal settlements, as described above.

Cash and Cash Equivalents

As of September 30, 2024, Y-mAbs had approximately $68.1 million in cash and cash equivalents. Cash utilized in the first three quarters of 2024 was $10.5 million, which was favorable relative to the Company’s internal forecasts, and is on track to meet its corporate guidance for the full year 2024.

2024 Financial Guidance

Management reiterates its full year 2024 guidance:

● Anticipated Total Net Revenues expected to be between $87 million and $95 million;
● Anticipated Operating Expenses expected to remain between $115 million and $120 million;
● Anticipated Total Annual Cash Investment expected to remain between $15 million and $20 million; and
● Cash and Cash Equivalents anticipated to continue to support operations as currently planned into 2027.

Webcast and Conference Call

Y-mAbs will host a conference call on Friday, November 8, 2024, at 8:00 a.m. ET. To participate in the call, please use the following dial-in information:

Investors (domestic):(877) 407-0792

Investors (international):(201) 689-8263

To access the live webcast, please use this link. Prior to the call and webcast, a slide presentation pertaining to the Company’s quarterly earnings will be made available on the Investor Relations section of the Y-mAbs website, www.ymabs.com, shortly before the call begins.