On November 4, 2024 TG Therapeutics, Inc. (NASDAQ: TGTX) (the Company or TG Therapeutics) reported its financial results for the third quarter of 2024, along with recent company developments and provided an update on 2024 revenue guidance (Press release, TG Therapeutics, NOV 4, 2024, View Source [SID1234647666]).

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Michael S. Weiss, the Company’s Chairman and Chief Executive Officer stated, "The positive feedback and uptake of BRIUMVI in the marketplace continues to outpace our expectations and we are excited to share with you the results of another quarter of growth and execution of our BRIUMVI launch and pipeline development. With $83.3 million of U.S. BRIUMVI net sales for the third quarter and continued strong commercial launch effort, we believe we are on a path for continued growth into the end of the year and into 2025 and further toward our long-term goal of becoming the number one prescribed anti-CD20 in terms of dynamic market share." Mr. Weiss continued, "Everyone at TG is focused on individuals living with relapsing forms of multiple sclerosis, and to that end, we continue to make strides with our clinical programs designed to improve their treatment experience, including shortening infusion times, minimizing infusion visits, offering a subcutaneous BRIUMVI option, and developing novel treatments such as our allogeneic CD19 CAR-T. We look forward to a strong close to 2024 and are excited for further progress in 2025 both commercially and clinically."

Recent Highlights & Developments

United States (U.S.) Commercialization of BRIUMVI (ublituximab-xiiy)

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BRIUMVI U.S. net product revenue of $83.3 million for the third quarter of 2024, reflecting approximately 15% quarter-over-quarter growth and over 230% growth from the same quarter last year.

BRIUMVI Clinical Data Presentations

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Presented updated data at the 2024 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting including:

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New five year data from the ULTIMATE I & II Phase 3 trials evaluating BRIUMVI in patients with relapsing forms of multiple sclerosis (RMS) which demonstrated that 92% of patients were free from disability progression after five years of treatment, an annualized relapse rate of 0.02 during year 5 of treatment (equivalent to one relapse occurring every fifty years of patient treatment), and an overall safety profile which remained consistent over 5 years of continuous treatment, with no new safety signals emerging with prolonged treatment.

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New data from the ENHANCE Phase 3b trial evaluating BRIUMVI in patients with RMS which demonstrated that:

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Rapid 30-minute BRIUMVI infusions are well tolerated with all infusion related reactions being mild (Grade 1) and resolving completed, and

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RMS patients who are already B-cell depleted can safely switch from a prior anti-CD20 therapy directly to 450 mg of BRIUMVI administered in 1 hour as an initial infusion, without a 150 mg initial dose, with 97% of infusions being completed without interruption or slowing.

Pipeline

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Initiated a phase 1 clinical trial evaluating subcutaneous ublituximab in RMS

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Received clearance by the U.S. Food and Drug Administration (FDA) of an Investigational New Drug (IND) application for azer-cel in progressive forms of multiple sclerosis (MS)

Manufacturing

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Secured FUJIFILM Diosynth Biotechnologies as a secondary US-based manufacturer of BRIUMVI out of its Holly Spring, North Carolina, United States, based facility.

2024 Updated Target U.S. BRIUMVI Guidance

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Raising BRIUMVI U.S. net product revenue target to $300 to $305 million for the full year 2024 (prior guidance of $290 to $300 million for full year 2024)

Remaining 2024 Development Pipeline Anticipated Milestones

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Study BRIUMVI in an additional autoimmune disease outside of MS

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Commence a clinical trial evaluating azer-cel in autoimmune diseases, starting with progressive MS

Financial Results for Third Quarter 2024

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Product Revenue, net: Product revenue, net was approximately $83.3 million and $206.4 million for the three and nine months ended September 30, 2024, respectively, compared to $25.1 million and $48.9 million for the three and nine months ended September 30, 2023, respectively. Product revenue, net for both the three and nine months ended September 30, 2024, and 2023, consisted of net product sales of BRIUMVI in the United States.

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License, milestone, royalty and other revenue: License, milestone, royalty and other revenue was approximately $0.6 million and $14.4 million for the three and nine months ended September 30, 2024, respectively, compared to $140.7 million and $140.8 million for the three and nine months ended September 30, 2023, respectively. License, milestone, royalty and other revenue for the nine months ended September 30, 2024, is predominantly comprised of a $12.5 million milestone payment under the Neuraxpharm Commercialization Agreement for the first key market commercial launch of BRIUMVI in the European Union (EU) which occurred in the first quarter of 2024. License, milestone, royalty and other revenue for the nine months ended September 30, 2023 is predominantly comprised of recognition of the one-time $140.0 million non-refundable upfront payment under the Commercialization Agreement with Neuraxpharm.

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R&D Expenses: Total research and development (R&D) expense was approximately $20.1 million and $70.4 million for the three and nine months ended September 30, 2024, respectively, compared to $14.8 million and $58.7 million for the three and nine months ended September 30, 2023, respectively. The increase in R&D expense during the three and nine months ended September 30, 2024 was primarily attributable to license and milestone expense related to the license agreement with Precision BioSciences, Inc., as well as additional manufacturing and development costs incurred in connection with our ublituximab subcutaneous development work during the period.

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SG&A Expenses: Total selling, general and administrative (SG&A) expense was approximately $42.0 million and $115.3 million for the three and nine months ended September 30, 2024, respectively, compared to $32.8 million and $91.6 million for the three and nine months ended September 30, 2023, respectively. The increase in both periods was primarily due to other selling, general and administrative costs, including personnel and consultants, associated with the commercialization of BRIUMVI during the period ended September 30, 2024.

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Net Income: Net income was $3.9 million and $0.1 million for the three and nine months ended September 30, 2024, respectively, compared to net income of $113.9 million and $27.1 million for the three and nine months ended September 30, 2023, respectively.

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Cash Position and Financial Guidance: Cash, cash equivalents and investment securities were $341.0 million as of September 30, 2024. We anticipate that our cash, cash equivalents and investment securities as of September 30, 2024, combined with the projected revenues from BRIUMVI, will be sufficient to fund our business based on our current operating plan.

CONFERENCE CALL INFORMATION

The Company will host a conference call today, November 4, 2024 at 8:30 AM ET to discuss the Company’s financial results from the third quarter ended September 30, 2024.

To participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics. A live audio webcast will be available on the Events page, located within the Investors & Media section, of the Company’s website at View Source An audio recording of the conference call will also be available for a period of 30 days after the call.

ABOUT BRIUMVI (ublituximab-xiiy) 150 mg/6 mL Injection for IV

BRIUMVI is a novel monoclonal antibody that targets a unique epitope on CD20-expressing B-cells. Targeting CD20 using monoclonal antibodies has proven to be an important therapeutic approach for the management of autoimmune disorders, such as RMS. BRIUMVI is uniquely designed to lack certain sugar molecules normally expressed on the antibody. Removal of these sugar molecules, a process called glycoengineering, allows for efficient B-cell depletion at low doses.

BRIUMVI is indicated in the U.S. for the treatment of adults with RMS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease and in the EU and UK for the treatment of adult patients with RMS with active disease defined by clinical or imaging features.

A list of authorized specialty distributors can be found at www.briumvi.com.

IMPORTANT SAFETY INFORMATION

Contraindications: BRIUMVI is contraindicated in patients with:

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Active Hepatitis B Virus infection

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A history of life-threatening infusion reaction to BRIUMVI

WARNINGS AND PRECAUTIONS

Infusion Reactions: BRIUMVI can cause infusion reactions, which can include pyrexia, chills, headache, influenza-like illness, tachycardia, nausea, throat irritation, erythema, and an anaphylactic reaction. In MS clinical trials, the incidence of infusion reactions in BRIUMVI-treated patients who received infusion reaction-limiting premedication prior to each infusion was 48%, with the highest incidence within 24 hours of the first infusion. 0.6% of BRIUMVI-treated patients experienced infusion reactions that were serious, some requiring hospitalization.

Observe treated patients for infusion reactions during the infusion and for at least one hour after the completion of the first two infusions unless infusion reaction and/or hypersensitivity has been observed in association with the current or any prior infusion. Inform patients that infusion reactions can occur up to 24 hours after the infusion. Administer the recommended pre-medication to reduce the frequency and severity of infusion reactions. If life-threatening, stop the infusion immediately, permanently discontinue BRIUMVI, and administer appropriate supportive treatment. Less severe infusion reactions may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

Infections: Serious, life-threatening or fatal, bacterial and viral infections have been reported in BRIUMVI-treated patients. In MS clinical trials, the overall rate of infections in BRIUMVI-treated patients was 56%, compared to 54% in teriflunomide-treated patients. The rate of serious infections was 5% compared to 3%, respectively. There were 3 infection-related deaths in BRIUMVI-treated patients. The most common infections in BRIUMVI-treated patients included upper respiratory tract infection (45%) and urinary tract infection (10%). Delay BRIUMVI administration in patients with an active infection until the infection is resolved.

Consider the potential for increased immunosuppressive effects when initiating BRIUMVI after immunosuppressive therapy or initiating an immunosuppressive therapy after BRIUMVI.

Hepatitis B Virus (HBV) Reactivation: HBV reactivation occurred in an MS patient treated with BRIUMVI in clinical trials. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with BRIUMVI. Do not start treatment with BRIUMVI in patients with active HBV confirmed by positive results for HBsAg and anti-HB tests. For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult a liver disease expert before starting and during treatment.

Progressive Multifocal Leukoencephalopathy (PML): Although no cases of PML have occurred in BRIUMVI-treated MS patients, JC virus infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies.

If PML is suspected, withhold BRIUMVI and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

MRI findings may be apparent before clinical signs or symptoms; monitoring for signs consistent with PML may be useful. Further investigate suspicious findings to allow for an early diagnosis of PML, if present. Following discontinuation of another MS medication associated with PML, lower PML-related mortality and morbidity have been reported in patients who were initially asymptomatic at diagnosis compared to patients who had characteristic clinical signs and symptoms at diagnosis.

If PML is confirmed, treatment with BRIUMVI should be discontinued.

Vaccinations: Administer all immunizations according to immunization guidelines: for live or live-attenuated vaccines, at least 4 weeks and, whenever possible, at least 2 weeks prior to initiation of BRIUMVI for non-live vaccines. BRIUMVI may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines during or following administration of BRIUMVI has not been studied. Vaccination with live virus vaccines is not recommended during treatment and until B-cell repletion.

Vaccination of Infants Born to Mothers Treated with BRIUMVI During Pregnancy: In infants of mothers exposed to BRIUMVI during pregnancy, assess B-cell counts prior to administration of live or live-attenuated vaccines as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines. Inactivated or non-live vaccines may be administered prior to B-cell recovery. Assessment of vaccine immune responses, including consultation with a qualified specialist, should be considered to determine whether a protective immune response was mounted.

Fetal Risk: Based on data from animal studies, BRIUMVI may cause fetal harm when administered to a pregnant woman. Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 B-cell depleting antibodies during pregnancy. A pregnancy test is recommended in females of reproductive potential prior to each infusion. Advise females of reproductive potential to use effective contraception during BRIUMVI treatment and for 6 months after the last dose.

Reduction in Immunoglobulins: As expected with any B-cell depleting therapy, decreased immunoglobulin levels were observed. Decrease in immunoglobulin M (IgM) was reported in 0.6% of BRIUMVI-treated patients, compared to none of the patients treated with teriflunomide in RMS clinical trials. Monitor the levels of quantitative serum immunoglobulins during treatment, especially in patients with opportunistic or recurrent infections, and after discontinuation of therapy, until B-cell repletion. Consider discontinuing BRIUMVI therapy if a patient with low immunoglobulins develops a serious opportunistic infection or recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.

Most Common Adverse Reactions: The most common adverse reactions in RMS trials (incidence of at least 10%) were infusion reactions and upper respiratory tract infections.

Physicians, pharmacists, or other healthcare professionals with questions about BRIUMVI should visit www.briumvi.com.

The full Summary of Product Characteristics approved in the European Union (EU) for BRIUMVI can be found here Briumvi | European Medicines Agency (europa.eu).

ABOUT BRIUMVI PATIENT SUPPORT in the U.S.

BRIUMVI Patient Support is a flexible program designed by TG Therapeutics to support U.S. patients through their treatment journey in a way that works best for them. More information about the BRIUMVI Patient Support program can be accessed at www.briumvipatientsupport.com.

ABOUT MULTIPLE SCLEROSIS

Relapsing multiple sclerosis (RMS) is a chronic demyelinating disease of the central nervous system (CNS) and includes people with relapsing-remitting multiple sclerosis (RRMS) and people with secondary progressive multiple sclerosis (SPMS) who continue to experience relapses. RRMS is the most common form of multiple sclerosis (MS) and is characterized by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. It is estimated that nearly 1 million people are living with MS in the United States and approximately 85% are initially diagnosed with RRMS.1,2 The majority of people who are diagnosed with RRMS will eventually transition to SPMS, in which they experience steadily worsening disability over time. Worldwide, more than 2.3 million people have a diagnosis of MS.

On November 4, 2024 Integra LifeSciences Holdings Corporation (NASDAQ: IART), a leading global medical technology company, reported financial results for the third quarter ending September 30, 2024 (Press release, Integra LifeSciences, NOV 4, 2024, View Source [SID1234647664]).

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Third Quarter 2024 Highlights
•Third quarter revenues of $380.8 million decreased 0.4% on a reported basis and 8.6% on an organic basis compared to the prior year. Revenue decreased 10.3% on an organic basis excluding Boston.

•Third quarter GAAP earnings per diluted share of $(0.14), compared to $0.24 in the prior year; adjusted earnings per diluted share of $0.41, compared to $0.76 in the prior year.

•Shipping holds communicated during the second quarter earnings call are releasing in line with expectations.

•Integra Skin production is on pace to meet historical revenue run rates for the fourth quarter.

•Updating full-year 2024 revenue guidance to a range of $1.609 billion to $1.619 billion and adjusted EPS guidance to a range of $2.41 to $2.49 per share.

•The Company announced Mojdeh Poul as Integra’s next president and chief executive officer.

"Our third-quarter results highlight the early progress we are making to identify and remediate the gaps in our quality management system," said Jan De Witte, president and CEO of Integra LifeSciences. "We are progressing with the implementation of our compliance master plan across our manufacturing and supply chain operations, which will position us to meet robust market demand and more consistently and reliably deliver to customers, patients, and shareholders."

Third Quarter 2024 Consolidated Performance

Total reported revenues of $380.8 million decreased 0.4% on a reported basis and 8.6% on an organic basis compared to the prior year. Revenue decreased 10.3% on an organic basis excluding Boston.
The Company reported GAAP gross margin of 52.6%, compared to 57.1% in the third quarter of 2023. Adjusted gross margin was 63.0%, compared to 64.6% in the prior year.
Adjusted EBITDA for the third quarter of 2024 was $61.8 million, or 16.2% of revenue, compared to $88.1 million, or 23.0% of revenue, in the prior year.
The Company reported a GAAP net loss of $(10.7) million, or $(0.14) per diluted share, in the third quarter of 2024, compared to GAAP net income of $19.5 million, or $0.24 per diluted share, in the prior year.

Adjusted net income for the third quarter of 2024 was $31.7 million, or $0.41 per diluted share, compared to $60.5 million, or $0.76 per diluted share, in the prior year.

Third Quarter 2024 Segment Performance
Codman Specialty Surgical (~70% of Revenues)
Total revenues were $270.8 million, representing reported growth of 1.0% and an organic decline of 10.7% compared to the third quarter of 2023.

•Sales in Neurosurgery declined 16.0% on an organic basis
◦The decline was driven primarily by temporary shipping holds in CSF management and Neuro monitoring, which have largely been resolved within the third quarter, as well as supply challenges in Dural access and repair
◦Advanced energy grew mid-single digits driven by CUSA capital and CUSA disposables
•Sales in Instruments grew 8.7% on an organic basis
•ENT reported revenue grew substantially due to the Acclarent acquisition

Tissue Technologies (~30% of Revenues)

Total revenues were $110.1 million, representing a reported decline of 3.6% and organic decline of 3.7% compared to the third quarter of 2023. Tissue Technologies sales were down 9.4% excluding sales of the Company’s products manufactured in Boston. Key drivers for the quarter include:

•Low double-digit decline in Integra Skin due to production challenges
•Low double-digit growth in DuraSorb, MicroMatrix and Cytal
•Sales in private label grew 13.3% on an organic basis

CEO Transition Update

Today, the Company announced Mojdeh Poul as Integra’s next president and chief executive officer. Ms. Poul succeeds Jan De Witte, who previously announced he will retire as president and chief executive officer. Ms. Poul will join Integra on January 6, 2025, at which time she will also be appointed to Integra’s board of directors.

Advancing our Strategy

•Continued strong demand for Integra’s diverse portfolio of leading brands
•Advancing the compliance master plan and investments in supply reliability
◦Neurosurgery shipping holds clearing in line with expectations
◦Integra Skin production is on pace to meet historical revenue run rates for the fourth quarter
•Began installing equipment in Braintree facility
•Continued integration success with the Acclarent ENT products
•Growth in DuraSorb and UBM portfolio remains strong

Balance Sheet, Cash Flow and Capital Allocation
The Company generated cash flow from operations of $22.5 million in the quarter. Total balance sheet debt and net debt at the end of the quarter were $1.81 billion and $1.54 billion, respectively, and the consolidated total leverage ratio was 4.0x.

As of quarter end, the Company had total liquidity of approximately $1.18 billion, including $277 million in cash plus short-term investments and the remainder available under its revolving credit facility.

2024 Outlook
For the fourth quarter 2024, the Company expects reported revenues in the range of $441 million to $451 million, representing reported growth of 11.1% to 13.6% and organic growth of 2.0% to 4.5%. Fourth quarter guidance reflects the integration of Acclarent, stepped up revenue from progress clearing the third-quarter shipping holds, improved production for Integra Skin, partially offset by additional quality holds. The Company expects adjusted EPS in a range of $0.81 to $0.89.

For the full year 2024, the Company is updating its revenue and adjusted EPS ranges of $1.609 billion to $1.619 billion and $2.41 to $2.49, respectively. The revenue range represents reported growth of 4.4% to 5.0% and organic growth of -1.7% to -1.0%.

The Company’s organic sales growth guidance for the fourth quarter and the full year excludes acquisitions and divestitures, as well as the effects of foreign currency.

Conference Call and Presentation Available Online
Integra has scheduled a conference call for 8:30 a.m. ET on Monday November 4, 2024, to discuss third quarter 2024 financial results and forward-looking financial guidance. The conference call will be hosted by Integra’s senior management team and will be open to all listeners. Additional forward-looking information may be discussed in a question-and-answer session following the call. Integra’s management team will reference a presentation during the conference call, which can be found on the Investor section of the website at investor.integralife.com.

A live webcast will be available on the Investors section of the Company’s website at investor.integralife.com. For those planning to participate on the call, register here to receive dial-in details and an individual pin. While not required, it is recommended to join 10 minutes prior to the event’s start. A webcast replay of the conference call will be available on the Investors section of the Company’s website following the call.

On November 4, 2024 Neogap Therapeutics, a Swedish clinical-stage biotechnology company, reported that it has entered a strategic collaboration with NorthX Biologics, a leading CDMO, to advance manufacturing strategies for Neogap’s personalised cancer cell therapy (Press release, Neogap Therapeutics, NOV 4, 2024, View Source [SID1234647663]). Supported by ongoing funding from the European Innovation Council (EIC) Accelerator, the partnership aims to optimise and scale production for future clinical trials.

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Neogap Therapeutics develops pTTL (personalised Tumour Trained Lymphocytes), a cell therapy designed to treat solid tumours by training the immune system to recognise and attack cancer cells through the patient’s unique neoantigens. Currently, pTTL is under evaluation in a Phase I/II clinical trial focused on assessing its safety and tolerability in patients with advanced colorectal cancer.

The collaboration, carried out within the framework of the EIC Accelerator program, aims to establish a robust, cost-effective production setup that enhances both productivity and scalability.

The project includes a comprehensive analysis of Neogap’s manufacturing protocols, with a focus on scale-out strategies and GMP process industrialisation to support large-scale clinical trials and eventual commercialisation. The goal is to implement streamlined production processes and logistics, increasing resilience and cost-effectiveness as Neogap progresses toward broader clinical applications and greater patient access.

Samuel Svensson, CEO of Neogap Therapeutics, comments: "Partnering with NorthX Biologics is an important step in preparing our therapy for future trials beyond the current Phase 1 study. Establishing a reliable and cost-effective manufacturing process is key to our clinical and commercial goals. We’re excited for our team to work closely with NorthX’s experts, combining our strengths to develop a scalable solution that will allow us to treat a larger patient population as we advance."

Janet Hoogstraate, CEO of NorthX Biologics, comments: "At NorthX Biologics, we are proud to be ‘beyond CDMO’ – a proactive partner that actively contributes to the development of future medicines by collaborating with innovative companies like Neogap Therapeutics. Through our close partnership, we leverage our expertise and Innovation Hub to support at every stage, from initial concept to scalable production of pioneering cell therapies. Together, we are driving groundbreaking innovations forward to improve patients’ lives around the world."

On November 4, 2024 ImmunoPrecise Antibodies Ltd. (the "Company" or "IPA") (NASDAQ: IPA),an AI-driven biotherapeutic research and technology company, reported the details of its upcoming TECHDAY event on Friday, November 15, 2024, from 9:00 a.m. to 12:30 p.m. EST in Cambridge, Massachusetts (Press release, ImmunoPrecise Antibodies, NOV 4, 2024, View Source [SID1234647660]). This exclusive gathering will highlight IPA’s latest advancements in AI-driven design, biologics innovation, and strategic technological developments.

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Highlights of TECHDAY:

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Presentation by Dr. Dirk Van Hyfte: Dr. Van Hyfte will present "Accelerating Drug Discovery with LENSai: A Comprehensive Solution." He will showcase LENSai, BioStrand’s revolutionary platform, and discuss how it transforms drug discovery by integrating biotechnology, biotherapeutics, and artificial intelligence. Key topics include using HYFT Universal Fingerprints to revolutionize multi-omics and data integration while accelerating drug discovery, development and optimization with AI-driven insights.
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LENSai Demo: A live demonstration of the LENSai platform, showcasing its capabilities in accelerating and enhancing the discovery and design of therapeutic antibodies through AI-driven insights.
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Presentation by Dr. Shuji Sato: Dr. Sato will present IPA’s B Cell Discovery Platform and discuss its integration with the company’s advanced AI and NGS workflows for highly efficient hit expansion. This process includes:
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Fast analysis of complete NGS repertoires
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Multimodal feature extraction that combines sequence, structure, and large language model (LLM) embeddings to deliver enhanced insights into sample diversity.
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Add-ons that complement outputs from phage display, B-cell, and hybridoma technologies, enabling the retrieval of antibody sequences with characteristics similar to known binders.
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Fireside Chat: Disruptive Dialogue: Empowering Drug Discovery Through Seamless Data Integration and AI-Powered Insights

Participants:

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Dr. Dirk Van Hyfte, Head of Innovation and Co-founder, BioStrand (IPA)
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Jeff Fried, Director of Platform Strategy and Innovation, InterSystems

This discussion will explore how vector search intelligence is at the core of the LENSai platform, seamlessly integrated with the InterSystems IRIS data platform to deliver precise, scalable solutions that accelerate antibody discovery, enhance accuracy, and increase candidate diversity.

AI-Driven Drug Discovery Summit USA 2024

Additionally, earlier that same week at the AI-Driven Drug Discovery Summit USA 2024, IPA will participate in another fireside chat titled Beyond conventional biologics: the intersection of machine learning and biological engineering to invent.

Participants at the AI-Driven Drug Discovery Summit USA 2024:

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Adam Root, Vice President and Head of Protein Sciences, Generate Biomedicines
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Dr. Dirk Van Hyfte, Head of Innovation and Co-founder, BioStrand (IPA)

The chat will focus on the integration of artificial intelligence and machine learning with wet lab infrastructure to accelerate biologics development.

A recorded webcast of the TECHDAY presentations will be available in the Investors section of the IPA website under "Events and Presentations" at ir.ipatherapeutics.com.

On November 4, 2024 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported a business update, and announced financial results for the third quarter ended September 30, 2024 (Press release, Ideaya Biosciences, NOV 4, 2024, View Source [SID1234647659]).

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"This was a transformational quarter for IDEAYA, including completion of an oversubscribed ~$302.4 million follow-on financing, a late breaker oral presentation at ENA 2024 for IDE397 in heavily pre-treated MTAP-deletion urothelial and lung cancer patients, and a successful Type C meeting with the FDA to enable a potential registration-enabling trial for darovasertib in neoadjuvant uveal melanoma. Next, we received IND clearance for Werner Helicase inhibitor IDE275 with our partner GSK, representing our fifth potential first-in-class clinical program," said Yujiro S. Hata, Chief Executive Officer and Founder, IDEAYA Biosciences. "We continue to execute on our strategic vision to build a leading precision medicine oncology pipeline, and are on track to nominate our 6th, 7th, and 8th development candidate by year-end, including from our B7H3/PTK7 bi-specific topo-ADC, MTAP-deletion, and KAT6 pathway programs. We look forward to highlighting IDEAYA’s potential first-in-class preclinical and clinical programs, and to continue to establish our scientific leadership in precision medicine oncology at our upcoming investor R&D day," said Michael White, Ph.D., Chief Scientific Officer, IDEAYA Biosciences.

"This past quarter, we made significant progress on the darovasertib program, including being ahead of our enrollment targets for the first-line MUM potential registration-enabling trial, and a successful Type C meeting with the FDA to inform a potentially registration-enabling trial in the neoadjuvant uveal melanoma setting. Next, the clinical data update from ENA 2024, provides further clinical proof-of-concept for IDE397 at the RP2D in MTAP-deletion urothelial and lung cancer. We are excited to advance our broader IDE397 rational combination strategy, including target expansion with AMG 193 in MTAP-deletion NSCLC in late 2024 to early 2025, and target expansion with Trodelvy (sacituzumab govitecan-hziy), Gilead’s Trop-2 directed antibody-drug conjugate, in MTAP-deletion urothelial cancer in the fourth quarter. Lastly, we are targeting to select a monotherapy expansion dose for IDE161, and achieve FPI in combination with Keytruda in MSI-High and MSS endometrial cancer by year-end," added Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

Summary of Q3 and Recent Key Developments

Research and Clinical Development

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Darovasertib in 1L MUM and Neoadjuvant Uveal Melanoma (UM)
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Enrollment in darovasertib + crizotinib 1L HLA-A2+ MUM potential Ph2/3 registration-enabling trial is ahead of schedule and has exceeded 150 patients
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Positive interim Phase 2 results of darovasertib (IDE196) from the company-sponsored and investigator-sponsored trials (IST) were highlighted during an Investor Webcast in September 2024, and over 75 patients have been enrolled in company-sponsored trial.
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Following a successful Type C meeting with the U.S. Food and Drug Administration (FDA), IDEAYA is finalizing the Phase 3 registrational trial protocol and is targeting to initiate its potential registration-enabling trial in the first half of 2025.
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IDE397 in MTAP-Deletion Solid Tumors
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Phase 1 expansion results of IDE397 in 27 evaluable MTAP-deletion urothelial cancer (UC) and non-small cell lung cancer (NSCLC) patients were presented as a late-breaking oral presentation at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium (ENA 2024) in Barcelona, Spain. Additional preclinical data on the anti-tumor activity by combinatorial inhibition of IDE397 and clinical stage PRMT5 inhibitors AMG 193 and BMS-986504 in MTAP-deleted tumors were included in a poster presentation.

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Reported positive interim data from 18 evaluable MTAP-deletion UC and NSCLC patients and selected the move-forward Phase 2 expansion dose (RP2D) in an Investor Webcast in July 2024.
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Enrollment is ongoing in the IDE397 and AMG 193 Phase 1 dose escalation, and targeting expansion in NSCLC in late 2024 to early 2025.
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Ongoing Phase 1 trial evaluating IDE397 in combination with Trodelvy in MTAP-deletion UC; targeting combination expansion in the fourth quarter of 2024. The PR reported at ENA 2024 has confirmed by RECIST 1.1.
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IDE161 in Tumors with Homologous Recombination Deficiency
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Targeting Phase 1/2 monotherapy expansion for IDE161 PARG inhibitor in priority solid tumor type(s) in the fourth quarter of 2024.
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Targeting first-patient-in for the Phase 1 trial evaluating IDE161, IDEAYA’s first-in-class potential PARG inhibitor, in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in MSI-High and MSS endometrial cancer (EC) in the fourth quarter of 2024.
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Preclinical data on IDE161 and antibody drug conjugate (ADC) combination rationale presented as a poster at ENA 2024.
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Received FDA IND clearance for IDE275 (GSK959), a potential first-in-class and best-in-class Werner Helicase inhibitor, for a Phase 1 trial in high microsatellite instability (MSI-High) tumors and earned a $7.0 million milestone from GSK.
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Targeting Development Candidate nomination for MTAP-deletion, KAT6 pathway and B7H3/PTK7 Topo-Payload Bispecific-ADC programs in the fourth quarter of 2024.
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IDEAYA is targeting to host a Virtual Investor R&D Day on Monday, December 16, 2024, to highlight IDEAYA’s potential first-in-class preclinical and clinical pipeline with management, leading Key Opinion Leader(s) (KOLs), and Pharma partner(s).

Corporate Development

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Raised gross proceeds of approximately $302.4 million in July 2024 through public offering, generating net proceeds of approximately $283.8 million.
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Appointed Douglas B. Snyder as Senior Vice President, General Counsel. Mr. Snyder brings over 25 years of legal experience with leading healthcare organizations, including GW Pharmaceuticals, Actelion Pharmaceuticals, Eisai, GSK, and the U.S. FDA.

Clinical Programs and Upcoming Milestones

Darovasertib (IDE196) Program in Tumors with GNAQ or GNA11 Mutations

Darovasertib is a potent and selective protein kinase C (PKC) inhibitor being developed to broadly address primary and metastatic UM. Darovasertib is currently being evaluated in four ongoing clinical trials. The darovasertib and crizotinib combination in MUM has FDA Fast Track designation:

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IDE196-002 (NCT05987332) is a Phase 2/3 potentially registration-enabling clinical trial of darovasertib + crizotinib in first-line human leukocyte antigens (HLA)-A2*02:01 negative (-) MUM. Over 150 patients enrolled as of October 31, 2024.

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IDE196-001 (NCT03947385) is a Phase 1/2 clinical trial of darovasertib + crizotinib in which we are planning to enroll additional HLA-A2*02:01 positive (+) patients.
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Phase 2 trials of darovasertib as neoadjuvant / adjuvant therapy in primary UM:
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IDE196-009 (NCT05907954) is a company-sponsored Phase 2 trial evaluating darovasertib as neoadjuvant treatment of UM prior to primary interventional treatment of enucleation or radiation therapy, and as adjuvant therapy following the primary treatment. Over 75 patients enrolled as of October 31, 2024.
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NADOM (NCT05187884) is a Phase 2 neoadjuvant / adjuvant trial of darovasertib in ocular melanoma. This is an IST led by Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent’s Hospital in Sydney with additional participating sites in Melbourne, Australia.
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Positive interim efficacy data from both the company-sponsored and the IST trials were highlighted during an Investor webcast in September 2024:
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31 enucleation and 18 plaque brachytherapy evaluable UM patients treated with darovasertib neoadjuvant therapy in Phase 2 company-sponsored and IST trials.
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~59% (29 of 49) of patients with >20% ocular tumor shrinkage by product of diameters.
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~49% (24 of 49) of patients with >30% ocular tumor shrinkage by product of diameters.
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~61% (19 of 31) eye preservation rate observed.
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Evidence of predicted visual preservation observed by reducing the amount of radiation associated with plaque brachytherapy.
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Manageable AE profile observed from Phase 2 company-sponsored trial (n=38), including 11% grade 3 or higher AEs, and 5% serious AE rate. The discontinuation rate observed was 3%. The most common AEs observed included diarrhea, nausea, vomiting and fatigue.
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IDEAYA had a successful Type C meeting with the FDA to discuss the clinical trial design for a registration-enabling Phase 3 trial in neoadjuvant UM patients. The planned trial aims to enroll approximately 400 patients in two cohorts: cohort 1 of plaque brachytherapy eligible UM patients, and cohort 2 of enucleation eligible UM patients. Cohort 1 will be randomized to darovasertib followed by plaque brachytherapy versus plaque brachytherapy alone, and cohort 2 will be randomized with or without darovasertib as neoadjuvant therapy. The primary endpoint of the trial is planned to be time to vision loss and eye preservation rate for cohort 1 and 2, respectively. The secondary endpoint for the trial is no detriment to Event-Free-Survival (EFS). Discussions with the FDA are ongoing regarding surrogate and composite endpoints to support earlier approval scenarios. IDEAYA is currently finalizing the trial protocol and is targeting to initiate the potential Phase 3 registration-enabling study in the first half of 2025.

IDE397 Program in Tumors with MTAP Deletion

IDE397 is a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2 alpha (MAT2A) in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion. IDEAYA continues to evaluate IDE397 in two trials in select monotherapy indications and in high conviction clinical combinations:

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IDE397-001 (NCT04794699) is a Phase 1/2 treatment study with a monotherapy expansion in MTAP-deletion UC and NSCLC. The estimated U.S. MTAP-deletion annual incidence in UC and NSCLC is approximately 48,000 patients.
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Encouraging clinical activity at the 30 mg once-a-day Phase 2 monotherapy expansion dose was observed in the Phase 1 clinical trial evaluating IDE397 in heavily pre-treated MTAP-deletion UC and NSCLC patients presented at ENA 2024 in October 2024. The patients evaluated had a median of two to three prior lines-of-therapy, ranging from one to seven. The reported Phase 1 clinical expansion data was based on 27 evaluable MTAP-deletion patients, including 10 UC, nine adenocarcinoma (Adeno) NSCLC, and eight squamous (Sq) NSCLC patients at the expansion dose of 30 mg once-a-day of IDE397 :
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~33% Overall Response Rate (ORR). One complete response (CR) and eight partial responses (PRs) by RECIST 1.1 evaluation out of 27 evaluable patients. Nine of nine responses have been confirmed by RECIST 1.1, including four UC patients, of which one was a CR, three squamous NSCLC patients, and two adenocarcinoma NSCLC patients. Two patients confirmed after the data cutoff date. In the earlier reported July 8, 2024, IDE397 webcast program update, five confirmed responses were reported out of 18 evaluable MTAP-deletion UC and NSCLC patients by RECIST 1.1. There were zero non-evaluable patients reported as of the data analysis.
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Confirmed ORR% by RECIST 1.1 by Solid Tumor Type: MTAP-deletion UC = 40% (4 of 10) confirmed ORR%; MTAP-deletion squamous NSCLC = ~38% (3 of 8) confirmed ORR%; MTAP-deletion adenocarcinoma NSCLC = ~22% (2 of 9) confirmed ORR%.
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Multiple confirmed partial responses by RECIST 1.1 harbor genetic co-alterations, including MTAP-deletion and KRAS G12D mutation in NSCLC, and MTAP-deletion and FGFR-TACC3 fusion in UC.
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~93% Disease Control Rate (DCR). One CR, eight PRs, and 16 stable disease (SD) by RECIST 1.1 evaluation out of 27 evaluable patients.
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Preliminary durability assessment: 15 of 27 patients still on treatment. Seven of nine RECIST 1.1 responses remain on treatment. Median duration of treatment (DOT) has not been reached and is greater than 6.2 months and median time to response (TTR) is ~2.7 months. The median duration of response and median progression free survival data is still immature. Three UC patients on treatment greater than 250 days, four squamous NSCLC patients on treatment greater than 200 days, and three adenocarcinoma NSCLC patients on treatment greater than 200 days
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~81% circulating tumor DNA (ctDNA) Molecular Response Rate (MRR). 17 of 21 patients with 50% or greater ctDNA reduction, and ~33% (7 of 21) with deep 90% or greater ctDNA reduction. All MRs (17 of 17) were rapid occurring at the first ctDNA sample analysis. There were several quality control failures of patient samples that led to unavailability for MR analysis
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Favorable adverse event (AE) profile. Approximately 18% grade 3 or higher drug-related AEs and no drug-related serious adverse events (SAEs) observed at the IDE397 30mg once-a-day expansion dose. No drug-related AEs leading to discontinuations were observed. We anticipate that the favorable AE profile and dosing convenience of a 30 mg once-a-day tablet has the potential to enable long-term dosing and combination development, including with MTA-cooperative PRMT5 inhibitors and topoisomerase payload antibody drug conjugates (ADCs)
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Over 35 global clinical trial sites activated in the U.S., Canada, Europe and Asia Pasic to enable rapid enrollment.
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Targeting development of IDE397 registrational plan in MTAP-deletion solid tumors in 2025.
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Phase 1/2 trial of IDE397 and AMG 193 in MTAP-Deletion NSCLC (Amgen-sponsored study, NCT05975073)
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Preclinical poster presentation on the antitumor activity by combinatorial inhibition of MAT2A and PRMT5 in MTAP-deleted tumors presented at ENA 2024.
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Enrollment is ongoing in the IDE397 and AMG193 Phase 1 dose escalation. Targeting expansion in NSCLC in late 2024 to early 2025.
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Phase 1 trial of IDE397 and Trodelvy in MTAP-deletion UC (IDEAYA-sponsored, NCT04794699) evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy is ongoing.
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Reported the first preliminary clinical case study of the IDE397 and Trodelvy combination in MTAP-deletion UC at ENA 2024, including a PR by RECIST 1.1 in a patient case report with a genetic co-alteration of MTAP-deletion and a FGFR3-TACC3 fusion, and rapid and deep first-evaluation molecular responses with ctDNA reduction of greater than 95% observed. The PR reported at ENA 2024 has now confirmed by RECIST 1.1.
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Targeting to initiate the IDE397 and Trodelvy Phase 1/2 combination expansion in MTAP-deletion UC in Q4 2024.
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Pursuant to the clinical study collaboration and supply agreement, IDEAYA and Gilead retain the commercial rights to their respective compounds, including with respect to use as a monotherapy or combination agent. IDEAYA is the study sponsor and Gilead will provide the supply of Trodelvy to IDEAYA.
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IDE397 monotherapy or in combination with Trodelvy has not been approved by any regulatory agency and the efficacy and safety of this combination has not been established.

IDE161 Program in Tumors with Homologous Recombination Deficiency

IDE161 is a potential first-in-class inhibitor of poly(ADP-ribose) glycohydrolase (PARG), a novel, mechanistically distinct target in the same clinically validated biological pathway as poly(ADP-ribose) polymerase (PARP). IDE161 received two FDA Fast Track designations in platinum-resistant advanced or metastatic ovarian cancer patients having tumors with BRCA1/2 mutations, and in pretreated advanced or metastatic HR+, Her2-, BRACA1/2 mutant breast cancer.

IDE161 is currently being evaluated in IDE161-001 (NCT05787587), a Phase 1 trial of IDE161 monotherapy in solid tumors with homologous recombination deficiency (HRD) and in the planned combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in microsatellite instability high (MSI-High) and microsatellite stable (MSS) endometrial cancer. Selection of an initial Phase 1/2 IDE161 monotherapy expansion dose in priority solid tumors type(s) is targeted in the fourth quarter of 2024. Separately, a first-patient-in for IDE161 in combination with KEYTRUDA is targeted in the fourth quarter of 2024. KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

In addition, preclinical results on IDE161 and ADC combination rationale were presented as a poster at ENA 2024.

GSK-Partnered Programs

IDE705 (GSK101) Program in Tumors with HRD

IDE705 (GSK101) is a potential first-in-class small molecule inhibitor of Pol Theta Helicase being developed as a combination treatment with niraparib for advanced solid tumors with HRD. The dose escalation portion of the GSK-sponsored Phase 1/2 clinical trial to evaluate GSK101 in combination with niraparib, the GSK small molecule inhibitor of PARP, for patients having solid tumors with BRCA or other HR mutations, or with HRD is currently ongoing.

Upon initiation of the Phase 1 dose expansion, IDEAYA will be eligible to receive a $10.0 million milestone payment, with the collaboration having potential further aggregate later-stage development and regulatory milestones of up to $465.0 million. GSK is responsible for all research and development costs for the program. Upon commercialization, IDEAYA will be eligible to receive up to $475 million of commercial milestones, and tiered royalties on global net sales of GSK101 – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

IDE275 (GSK959) Program in Tumors with MSI-High
IDE275 (GSK959) is a potential first-in-class Werner helicase inhibitor that received FDA IND clearance for a Phase 1 trial in October 2024. The GSK-sponsored Phase 1 trial will evaluate IDE275 (GSK959) in patients having MSI-High tumors, as a monotherapy and in combination with a PD-1 inhibitor.

IDEAYA earned a $7 million milestone payment for the IND clearance and has the potential to earn up to an additional $10.0 million upon initiation of Phase 1 clinical dose expansion. In addition, IDEAYA is entitled to receive up to $465.0 million in further later-stage development and regulatory milestones. GSK is responsible for 80% of global research and development costs and IDEAYA is responsible for 20% of such costs. Upon commercialization, IDEAYA will be eligible to receive up to $475 million of commercial milestones, 50% of U.S. net profits and tiered royalties on global non-U.S. net sales of the Werner Helicase inhibitor development candidate (DC) – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

B7H3/PTK7 Topo-Payload BsADC Program

IDEAYA entered into an option and license agreement for a potential first-in-class B7H3/PTK7 Topo-Payload BsADC program with Biocytogen in July 2024. The agreement grants IDEAYA an option for an exclusive worldwide license from Biocytogen for a potential first-in-class B7H3/PTK7 Topo-Payload BsADC program. B7H3/PTK7 has been found to be co-expressed in multiple solid tumor types, including double-digit percent prevalence in lung, colorectal, and head and neck cancers, among others. Based on preclinical data, the potential first-in-class B7H3/PTK7 Topo-Payload BsADC program has the potential to be developed as a monotherapy agent and used in combination with multiple programs in IDEAYA’s pipeline targeting DDR-based therapies, including the PARG inhibitor IDE161. A development candidate nomination for the B7H3/PTK7 Topo-Payload BsADC program is targeted in the fourth quarter of 2024.

Next-Generation Precision Medicine Pipeline Programs

Early preclinical research programs focused on pharmacological inhibition of several new targets for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures are ongoing. These programs have the potential for discovery and development of first-in-class or best-in-class therapeutics with multiple wholly owned DC nominations targeted in the fourth quarter of 2024, including in MTAP-deletion solid tumors indications to enable a potential wholly-owned clinical combination with IDE397, and separately a DC nomination in the lysine acetyltransferase 6 (KAT6) pathway.

Financial Results

As of September 30, 2024, IDEAYA had cash, cash equivalents and marketable securities totaling $1.2 billion. This compared to cash, cash equivalents and marketable securities of $952.7 million as of June 30, 2024. The increase was primarily attributable to $283.8 million in net proceeds from the underwritten public offering of common stock and pre-funded warrants to purchase common stock in July 2024, partially offset by net cash used in operations.

Research and development (R&D) expenses for the three months ended September 30, 2024 totaled $57.2 million compared to $54.5 million for the three months ended June 30, 2024. The increase was primarily due to clinical trial and outside services expenses.

General and administrative (G&A) expenses for the three months ended September 30, 2024 totaled $9.7 million compared to $10.4 million for the three months ended June 30, 2024. The decrease was primarily due to stock-based compensation expense.

The net loss for the three months ended September 30, 2024 was $51.8 million compared to the net loss of $52.8 million for the three months ended June 30, 2024. Total stock compensation expense for the three months ended September 30, 2024 was $9.2 million compared to $9.7 million for the three months ended June 30, 2024.