Exelixis prelims, guidance

 – Cabozantinib franchise achieves approximately $1.805 billion in preliminary U.S. net product revenues for fiscal year 2024 –

– Fiscal year 2025 net product revenues guidance of $1.95 billion - $2.05 billion –

– Presentation and webcast at 43rd Annual J.P. Morgan Healthcare Conference tomorrow, Monday, January 13th at 5:15 p.m. PT / 8:15 p.m. ET –

Preliminary Fiscal Year 2024 Financial Results & 2025 Financial Guidance

Exelixis is providing the following preliminary unaudited 2024 financial results and financial guidance for 2025. Net product and total revenues guidance do not currently reflect any revenues resulting from a potential U.S. regulatory approval and commercial launch of CABOMETYX® (cabozantinib) for the treatment of patients with previously treated advanced neuroendocrine tumors (NET). The U.S. Food and Drug Administration (FDA) is currently reviewing Exelixis' supplemental New Drug Application (sNDA) for this proposed indication, with a Prescription Drug User Fee Act (PDUFA) target action date of April 3, 2025.

	Fiscal Year 2024	Fiscal Year 2025 Guidance
Total revenues	~ $2.165 billion	$2.15 billion - $2.25 billion
Net product revenues	~ $1.805 billion	$1.95 billion - $2.05 billion(1)
Cost of goods sold	~ 4.2%	4% - 5% of net product revenues
Research and development expenses	~ $910 million(2)	$925 million - $975 million(3)
Selling, general and administrative expenses	~ $495 million(4)	$475 million - $525 million(5)
Effective tax rate	n/a(6)	21% - 23%
Ending cash and marketable securities(7)	~ $1.75 billion	n/p

(1)		Exelixis’ 2025 net product revenues guidance range includes impact of a U.S. wholesale acquisition cost increase of 2.8% for CABOMETYX effective Jan. 1, 2025.
(2)		Includes $30.7 million of non-cash stock-based compensation expense.
(3)		Includes $40.0 million of non-cash stock-based compensation expense.
(4)		Includes $63.2 million of non-cash stock-based compensation expense.
(5)		Includes $60.0 million of non-cash stock-based compensation expense.
(6)		Preliminary results not yet available.
(7)		Cash and marketable securities are composed of cash, cash equivalents and marketable securities. Fiscal year 2025 guidance not provided (n/p).

The preliminary 2024 financial information presented in this press release has not been audited and is subject to change. The complete Exelixis Fourth Quarter and Fiscal Year 2024 Financial Results are planned for release after market on Tuesday, February 11, 2025.

“Entering 2025, Exelixis stands at an inflection point as we work toward our goal of building a multi-product, multi-franchise oncology business,” said Michael M. Morrissey, Ph.D., President & CEO, Exelixis. “Exelixis had a very successful 2024 highlighted by strong commercial and financial performance, the favorable ruling on our cabozantinib patent litigation, accelerating progress with the zanzalintinib pivotal trial program and establishing our zanzalintinib clinical development collaboration with Merck. We’re carrying that momentum into the new year as we seek to grow cabozantinib franchise revenues, accelerate and expand our zanzalintinib pivotal development program, and advance our diversified therapeutic pipeline of small molecules and biotherapeutics.”

Dr. Morrissey continued: “We expect 2025 to be a year of regulatory, clinical and commercial execution as we work toward a potential regulatory approval and launch for cabozantinib in neuroendocrine tumors and prepare for multiple zanzalintinib and pipeline data readouts throughout the year. As cabozantinib’s commercial success drives the business forward in the near-term, we’re excited by zanzalintinib’s potential to surpass cabozantinib’s scope and scale in the coming years and to become an important component of our mid- and long-term revenue growth. We’re also optimizing our earlier stage pipeline, rapidly profiling compounds and advancing only those with the highest probability of success into full development. We look forward to providing more detailed updates on our pipeline progress at an R&D Day later this year. Finally, we’ll maintain our balanced approach to capital allocation, leveraging our strong balance sheet to execute on business development opportunities within the GU and GI oncology space, while using free cash flows to fund our stock repurchase program and return capital to shareholders.”

Corporate Updates

Stock Repurchase Program Update. In August 2024, Exelixis announced that the company’s Board of Directors authorized the repurchase of up to $500 million of the company’s common stock through the end of 2025, the third stock repurchase program undertaken by Exelixis since March 2023. Under this program, as of the end of fiscal year 2024, Exelixis has repurchased $205.6 million of the company’s common stock, at an average price of $33.62 per share.

Presentation and Webcast

Exelixis President and Chief Executive Officer Michael M. Morrissey, Ph.D., will provide a corporate overview and discuss the company’s preliminary fiscal year 2024 financial results, 2025 financial guidance and key priorities and milestones for 2025 during the company’s presentation at the 43rd Annual J.P. Morgan Healthcare Conference beginning at 5:15 p.m. PT / 8:15 p.m. ET on Monday, January 13, 2025.

To access the webcast link, log onto www.exelixis.com and proceed to the Event Calendar page under the Investors & News heading. A replay will also be available at the same location for at least 30 days.

https://www.businesswire.com/news/home/20250112148606/en/

New US Rule Aims to Block China's Access to AI Chips and Models by Restricting the World

 The Biden administration announced a bold and controversial new export control scheme today, designed to prevent the advanced chips and artificial intelligence models themselves from ending up in the hands of adversaries such as China.

The administration’s new “AI Diffusion rule” divides the world into nations that are allowed relatively unfettered access to America’s most advanced AI silicon and algorithms, and those that will require special licenses to access the technology. The rule, which will be enforced by the Commerce Department’s Bureau of Industry and Security, also seeks to restrict the movement of the most powerful AI models for the first time.

“The US leads the world in AI now, both AI development and AI chip design, and it's critical that we keep it that way,” the US Commerce Secretary Gina Raimondo said ahead of today’s announcement.

The list of trusted nations are the UK, Canada, Australia, Japan, France, Germany, Belgium, Denmark, Finland, Ireland, Italy, the Netherlands, New Zealand, Norway, Republic of Korea, Spain, Sweden and Taiwan.

Companies in other nations not subject to arms controls will be able to obtain up to 1,700 of the latest AI chips without special permission, the rule states. They will be able to apply for a special license to acquire more chips, to build very large scale datacenters using US technology, or to gain access to the most powerful closed model “weights” made by US firms. Companies will be required to have adequate physical and cyber-security to obtain a license.

Supply chain activities, including the design, manufacturing, and storage of chips will be exempt from the rule. The rule also will not restrict open source AI models such as Meta’s Llama, the administration says.

Arms embargoed nations such as China, Iran, and North Korea are already forbidden from obtaining advanced chips. The new rule will for the first time restrict their access to advanced models.

“The semiconductors that power [AI] and the model weights are, as we all know, a dual use technology,” Raimondo added ahead of the announcement. “They're used in many commercial applications, but also can be used by our adversaries to run nuclear simulations, develop bio weapons and advance their militaries.”

The rule is sure to stoke controversy, however, because it may throttle international sales of AI at a critical moment for the industry. It comes just a week before Trump’s inauguration. The ruling sets a 120 day consultation period, meaning Donald Trump‘s administration will be expected to listen to input, perhaps modify the rule, and then enforce it.

Nvidia, the world’s leading manufacturer of AI chips, called the rule “unprecedented and misguided” in a blog post. “While cloaked in the guise of an ‘anti-China’ measure, these rules would do nothing to enhance US security. Rather than mitigate any threat, the new Biden rules would only weaken America’s global competitiveness, undermining the innovation that has kept the US ahead.”

The US already limits exports of advanced AI chips to China, a key geopolitical rival, but companies there have been able to build cutting algorithms using computer clusters located in other nations. Under the new rule, China will not be able to build so-called frontier AI models in other nations impacted by the rule.

The rule is the latest in an escalating series of export controls aimed at preventing China from harnessing cutting edge AI. The technology is expected to become increasingly crucial for military, intelligence, and industrial applications that could define geopolitical power in the decades to come. The Biden administration introduced new restrictions on the export of chip-manufacturing equipment, certain types of computer memory, and chip design software to China in December in its latest effort to weaken the country’s ability to mint advanced chips.

Biden officials say that they found this rule necessary because AI may advance swiftly and unpredictably in the years to come. “The US has to be prepared for rapid increases in AI capabilities in the coming years, which could have transformative impacts on the economy and on our national security,” said Jake Sullivan, the Biden administration’s National Security Advisor.

The Biden administration also felt justified in setting the rules in its last days because of how rapidly Chinese AI is advancing, according to a senior administration official who asked not to be named. The administration believes China’s AI development is between six and 18 months behind that of the US. “Time is really of the essence,” the official said of the rule. “We believe we're in a critical window right now.”

https://www.wired.com/story/new-us-rule-aims-to-block-chinas-access-to-ai-chips-and-models-by-restricting-the-world/

Insilico Medicine licenses 2nd AI-generated cancer drug candidate to Menarini’s Stemline in $550M deal

 Another new year, another half-billion-biobuck transaction between Insilico Medicine and the Italian drugmaker Menarini Group.

Following a licensing agreement last January—which saw Menarini’s Stemline Therapeutics subsidiary pick up an artificial intelligence-designed breast cancer therapy candidate from Insilico for $12 million upfront and more than $500 million tied to its future successes—the two companies are at it again with a similar deal.

Their second exclusive, global in-licensing covers a second small molecule inhibitor, this time targeting what they described as a variety of solid tumors. According to Insilico and Stemline, the potential drug has successfully completed preclinical testing.

This time, the new deal includes $20 million paid upfront, with more than $550 million linked to clearing development, regulatory and commercial milestones.

“We are thrilled to enter our second collaboration with Insilico Medicine, a leader in the field of generative AI, for a highly selective and potentially best-in-class small molecule targeting a broad range of cancers,” Menarini CEO Elcin Barker Ergun said in a statement. “This asset will help us enter into new areas of high unmet need, expanding the tumor areas where we can help cancer patients with ground-breaking therapies.”

Insilico—a former Fierce Medtech Fierce 15 and Fierce 50 winner—designed the new asset using its Chemistry42 platform for generating druglike compounds. As was the subject of last year’s deal, MEN2312, which aims to inhibit transcription of KAT6 and block the estrogen receptors of breast cancer cells, with the goal of overcoming the tumor’s resistance to endocrine-based therapies.

Stemline has said it is currently evaluating MEN2312 as a single agent and in combination with standard-of-care treatments in patients with metastatic ER+/HER2- breast cancer.

“Our previous experience with Menarini Stemline proved that the company is efficient, agile, strategic, and committed to rapidly delivering the best novel therapeutic solutions to patients with cancer, maximizing the probability of success of the program,” said Insilico’s founder and CEO Alex Zhavoronkov, Ph.D.

https://www.fiercebiotech.com/medtech/insilico-medicine-licenses-2nd-ai-generated-cancer-drug-candidate-menarinis-stemline-550m

JPM25, Day 1: GSK’s billion-dollar bet, Bayer’s trial first, more

 The J.P. Morgan Healthcare Conference in San Francisco is back for 2025 and here at Fierce Biotech, we’re going to bring you all the latest updates live from the life sciences event of the year.

As is tradition, we’ve already had a few notable mid-range deals and some bumper biotech fund raises in the week leading up to the event. This included Lonza's Synaffix adding Boehringer to its constellation of partners with a $1.3 billion ADC tech pact, with Roche following suit in that space, penning a potential $780 million ADC deal with Chugai, as Sanofi inked a $400 million biobucks pact with Alloy’s antisense platform.

There was also a major $410 million venture raise for oral GLP-1 player Verdiva as neurological focused Tenvie launched with a cool $200 million.

But where the biotech gods giveth, they also taketh away. There was some major pruning across multiple biotechs, including for Intellia, Galapagos, Cassava, Scribe IGM, Y-mAbs and Passage Bio, as they streamline into 2025.

What can we expect from the conference itself? The Fierce team will be on the ground hunting down the biggest announcements and interviews, as well as running our own events, so stay tuned.

Check out our daily updates below for all the latest from JPM today and come back each day this week for your roundups.

Monday 4:30 a.m. ET Jan. 13

Tune Therapeutics enters the JPM dance floor with a bumper $175 million series B raise for its epigenetic silencing drug against chronic hepatitis B. Story. 

Monday 2:30 a.m. ET Jan. 13

German pharma Bayer also comes out the gates at pace with news that its BlueRock Parkinson’s disease cell therapy is moving into late-stage testing, with that trial set to be the first registrational phase 3 for an investigational allogeneic cell therapy in the area. 

Monday 2:00 a.m. ET Jan. 13

GSK clearly wanted an early run at the news cycle, sending word early Monday morning that it had tied up a GI cancer buyout deal with biotech IDRx worth up to $1.15 billion. Story. 

Saturday 6:00 a.m. ET Jan. 10

Gilead roared into JPM25 with a major $1.7 billion deal, that includes a huge $250 million upfront, for access to Leo Pharma's preclinical inflammation drugs. Story. 

https://www.fiercebiotech.com/biotech/jpm25-day-1-fierce-biotech-daily-roundup

5 Novel FDA Approvals Notched in 2024

 

Among the 55 novel drugs that crossed the regulatory finish line last year were notable new mechanisms of action, coming particularly in the oncology and neurosciences spaces.

The FDA approved 55 novel medicines in 2024—some first-in-class and others representing the first new mechanism of action for an indication in decades.

Novel approvals last year ran the therapeutic gamut from cardiovascular and hematological to infectious diseases, with some of the most significant new mechanisms of action found in oncology and neuroscience.

Top of mind is Bristol Myers Squibb’s Cobenfy, which the FDA greenlit in September as the first novel schizophrenia treatment in 35 years. Going back to February, we saw the approval of Iovance’s Amtagvi, the first one-time cell therapy for a solid tumor and the first tumor-infiltrating lymphocytes (TIL) therapy. Amtagvi is indicated for advanced melanoma, which has been notoriously difficult to treat. Another notable milestone was the March approval of Madrigal Pharmaceuticals’ Rezdiffra, the first therapy to get the FDA’s nod for metabolic dysfunction-associated steatohepatitis (MASH).

Here’s a look at five of the year’s most notable novel approvals.

Iovance’s Amtagvi Jumpstarts TIL Space

In February 2024, the FDA granted accelerated approval to Iovance Biotherapeutics for Amtagvi to treat patients with advanced melanoma. Forty years in the making, TIL therapies take advantage of the patient’s own immune cells—lymphocytes—which tend to be suppressed in the tumor environment. These cells are extracted from tumor biopsies, expanded in numbers or revamped for better efficacy, then transfused back into the patient, leading to antitumor activity.

Iovance supported its Biologics License Application for Amtagvi with clinical data showing a 31% objective response rate with a median duration of response not reached at 18.6 months of follow-up; 42% of responses lasted for two years or longer.

While CAR T therapies have transformed treatment for blood cancers, their performance hasn’t been as impressive against solid tumors. Part of the attraction of TIL therapies is their ability to recognize multiple antigens simultaneously, something CAR Ts are unable to do. Conventional CAR Ts can only recognize a small number of proteins on the surface of tumor cells, while TILs can identify tumor targets derived from intra- or extracellular tumor proteins, Sammy Farah, CEO of Turnstone Biologics, told BioSpace in February. Because solid tumors are known to be heterogeneous, TILs are likely to be successful as a treatment modality, Farah said.

With more than 75 TIL immunotherapies in preclinical or clinical studies for various indications, numerous players are coming up behind Iovance. Turnstone Biologics is developing TIL therapies for colorectal cancers, head and neck squamous cell carcinoma and uveal melanoma, while Instil Bio is working on TILs for non-small cell lung cancer and other solid tumors. Bristol Myers Squibb and Incyte Corporation are also active in this space.

Adaptimmune’s Tecelra Succeeds Against Synovial Sarcoma

Also in the cell therapy space, Adaptimmune Therapeutics in August 2024 secured FDA approval for the first engineered T cell therapy for solid tumor cancers in the U.S. Tecelra is also the first new therapeutic option for synovial sarcoma—a rare soft tissue cancer—in more than 10 years. Like Amtagvi, Tecelra was approved under the FDA’s accelerated pathway.

Also similar to Amtagvi, Tecelra leverages the patient’s immune cells and modifies them to be able to target cancer cells. Tecelra is specifically designed to recognize and attack the melanoma-associated antigen A4 (MAGE-A4) protein, which is crucial to preventing cell cycle arrest and cell death. MAGE-A4 is commonly overexpressed in solid tumors, especially synovial sarcoma.

The FDA’s approval was based on results of the SPEARHEAD-1 study, in which treatment with Tecelra led to an overall response rate of 43%. A complete response was reported in 4.5% of patients. Treatment response lasted for at least 12 months in 39% of study participants who were responsive to the therapy.

Bristol Myers Squibb’s Cobenfy Breaks Through Against Schizophrenia

On the neuro front was the FDA’s approval of Bristol Myers Squibb’s Cobenfy in September. A first-in-class muscarinic agonist, Cobenfy comprises two separate drugs with distinct mechanisms of action: xanomeline activates M1 and M4 muscarinic receptors to reduce schizophrenia symptoms, while trospium reduces potential side effects of such activation, such as cardiovascular issues and increased production of saliva and tears. Dopamine-based drugs come with side effects such as weight gain and drowsiness. Targeting the muscarinic pathway may avoid such issues because these receptors are not expressed in key brain regions, Carlos Dortrait, SVP and general manager of U.S. immunology and neuroscience at BMS, told BioSpace in September.

BMS supported Cobenfy’s application with data from three registrational studies. EMERGENT-1 and EMERGENT-2 established the drug’s efficacy in treating schizophrenia on the Positive and Negative Syndrome Scale, and EMERGENT-3 showed that the therapy, then called KarXT, could significantly reduce overall symptom severity.

While Cobenfy proved the potential of targeting the muscarinic pathway in schizophrenia, the mechanism was called into question not two months later when AbbVie’s emraclidine failed to show efficacy in two Phase II clinical trials for the neuropsychiatric disease. The difference might lay in the M1 receptor, Stifel analysts suggested in November. While Cobenfy acts on both the M1 and M4 receptors, emraclidine only targets M4. “There’s been a longstanding thesis that M1 may contribute to efficacy on cognition,” the analysts wrote.

If true, this would be bad news for Neurocrine Biosciences, which is developing a muscarinic M4 selective agonist, NBI-1117568. The San Diego–based company announced results from a mid-stage trial of the candidate in August 2024, showing that the lowest dose of NBI-1117568 improved symptoms of schizophrenia. All other doses failed to meet the study’s primary endpoint.

Roche’s Tecentriq Hybreza Provides Flexible Treatment Option

Also in September, the FDA greenlit the first subcutaneous PD-(L)1 blocker in the U.S., Roche’s Tecentriq Hybreza. Approved for the same indications as intravenous Tecentriq—including skin, liver, lung and soft-tissue cancers—the subcutaneous formulation leverages Halozyme Therapeutics’ Enhanze technology, which uses a recombinant enzyme to digest hyaluronan proteins beneath the skin to improve fluid flow in the subcutaneous space. This effect allows large volumes of the liquid Tecentriq to be injected under the skin, while also boosting the medicine’s dispersion and absorption.

Tecentriq Hybreza “can treat patients faster and in more accessible settings” and “offers patients with multiple cancer types and their physicians greater flexibility and choice of treatment administration,” Roche CMO Levi Garraway said in a statement following the approval.

The subcutaneous formulation is administered in approximately seven minutes, while an intravenous infusion of Tecentriq usually takes 30 minutes to 60 minutes, according to Roche.

Approval of Tecentriq Hybreza was based partly on the Phase Ib/III IMscin001 study, in which the subcutaneous injection reached comparable levels of the drug in the blood as its intravenous formulation, with similar safety and efficacy profiles.

ARS Pharmaceuticals’ Neffy First Nasal Spray for Severe Allergies

People living with severe allergic reactions that could lead to anaphylaxis got a new, more palatable treatment option in August when the FDA approved ARS Pharmaceuticals’ Neffy as the first nasal spray for the condition. The first epinephrine product for the treatment of anaphylaxis that is not administered by injection, Neffy is a single-dose nasal spray administered into one nostril. A second dose may be administered if there is no improvement in symptoms or symptoms worsen, according to the FDA’s approval announcement.

“Anaphylaxis is life-threatening and some people, particularly children, may delay or avoid treatment due to fear of injections,” Kelly Stone, associate director of the Division of Pulmonology, Allergy and Critical Care in the FDA’s Center for Drug Evaluation and Research, said in a statement. “The availability of epinephrine nasal spray may reduce barriers to rapid treatment of anaphylaxis.”

Neffy’s approval was supported by four studies in 175 healthy adults without anaphylaxis, which showed comparable epinephrine blood concentrations between the nasal spray and approved epinephrine injection products. Neffy also led to similar increases in blood pressure and heart rate as epinephrine injection products did. These physiological changes are critical effects of epinephrine in the treatment of anaphylaxis, according to the FDA.

https://www.biospace.com/fda/5-novel-fda-approvals-notched-in-2024