On June 24, 2025 Hoth Therapeutics reported it will host a Key Opinion Leader (KOL) event on, at 3:30PM EST to highlight recent clinical progress with HT-001, a novel topical therapeutic developed to address EGFR inhibitor-induced skin toxicities in cancer patients (Press release, Hoth Therapeutics, JUN 24, 2025, View Source [SID1234654095]). This event will feature insights from derm-oncology and dermatology specialists Jonathan Hale Zippin M.D., Ph.D., and Adam Friedman M.D., F.A.A.D., who will present interim results from the ongoing Phase 2 trial and discuss how HT-001 could redefine supportive care standards for oncology patients. Access/join the event through the following link: View Source

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Phase 2a Trial Highlights (CLEER-001)

100% of enrolled patients in open-label cohort achieved at least one primary endpoint of clinical dermatologic improvement
Over 65% reported reductions in pain and pruritus (itching)
0% required dose reduction or discontinuation of their EGFRI therapy.
Topical therapy was well tolerated with no serious adverse events.
NEW YORK, June 24, 2025 /PRNewswire/ — Hoth Therapeutics, Inc. (NASDAQ: HOTH), a clinical-stage biopharmaceutical company developing targeted therapies for rare and serious inflammatory conditions, reported that its investigational candidate HT-001 met the primary efficacy endpoint in at least one metric in 100% of patients in its ongoing Phase 2a clinical study (CLEER-001) evaluating treatment for epidermal growth factor receptor inhibitor (EGFRI)-induced cutaneous toxicities.

EGFR inhibitors, used widely to treat non-small cell lung cancer (NSCLC), pancreatic, breast, colorectal, and head and neck cancers, are associated with dermatologic side effects in up to 90% of patients, often resulting in painful rashes, pruritus, dryness, nail changes, and alopecia. These adverse events frequently force dose reductions or treatment discontinuation, limiting therapeutic efficacy and patient outcomes.

"HT-001 is a breakthrough candidate with the potential to be the first FDA-approved therapy specifically targeting these EGFRI-related skin toxicities," said Robb Knie, CEO of Hoth Therapeutics. "The ability to preserve full-dose cancer treatment while improving patient quality of life addresses a critical unmet need across oncology."

Phase 2a Trial Highlights (CLEER-001)

100% of enrolled patients in open-label cohort achieved at least one primary endpoint of clinical dermatologic improvement
Over 65% reported reductions in pain and pruritus (itching)
0% required dose reduction or discontinuation of their EGFRI therapy.
Topical therapy was well tolerated with no serious adverse events.
HT-001 is a once-daily topical gel formulated with an FDA-approved neurokinin-1 receptor antagonist (NK1RA). This mechanism mitigates inflammatory pathways triggered by EGFR inhibition, particularly Substance P-driven responses that lead to skin breakdown. By targeting the neuroinflammatory axis, HT-001 reduces symptoms without immunosuppression or systemic toxicity.

Supporting Preclinical Data

In preclinical rat models co-treated with erlotinib (5.85 mg/kg/day), HT-001 significantly reduced:

Dermatitis and alopecia severity
Inflammatory markers including Substance P and neutrophil activity
Disease progression even when HT-001 was introduced after symptom onset.
Additionally, in compassionate-use human cases, complete symptom resolution was observed within one week, with no recurrence for up to three weeks post-treatment discontinuation.

Regulatory and Development Pathway

HT-001 is being advanced under the 505(b)(2) regulatory pathway, enabling the use of existing safety data to accelerate development. Key milestones include:

IND opened and chronic toxicology completed.
Phase 2a trial (CLEER-001) currently underway in the U.S.
Phase 2b/3 trial planning in progress

On June 24, 2025 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, reported that the first patient has been dosed in VS-7375-101, the U.S. Phase 1/2a clinical trial evaluating VS-7375, a potential best-in-class oral KRAS G12D (ON/OFF) inhibitor, in patients with advanced KRAS G12D mutant solid tumors (Press release, Verastem, JUN 24, 2025, View Source [SID1234654094]).

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"We continue to make strong progress against our strategic priorities and key milestones that we set at the beginning of the year, including our recent FDA approval and commercial launch and our positive updated results and trial expansion in first-line metastatic pancreatic cancer. We are now excited to have achieved another milestone with the initiation of our first clinical trial and first patient dosed with VS-7375, a potential best-in-class oral KRAS G12D (ON/OFF) inhibitor, in the U.S.," said Dan Paterson, president and chief executive officer of Verastem Oncology.

VS-7375-101 is a Phase 1/2a study being conducted in the U.S., with plans to expand globally, and will evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The monotherapy dose escalation phase of the study will use a starting dose of 400 mg, based on an efficacious dose identified in the Phase 1/2 study conducted in China by the Company’s partner, GenFleet Therapeutics. GenFleet announced encouraging initial safety and efficacy results from its Phase 1 dose-escalation phase of its study of VS-7375 (known as GFH375 in China) at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting. Verastem plans to dose-escalate across dose levels where encouraging initial safety and efficacy were observed in patients with advanced KRAS G12D mutant solid tumor cancers in GenFleet’s study. Upon successful completion of the dose-escalation phase, the Company will select a recommended Phase 2 dose and assess the efficacy and safety of monotherapy VS-7375 in expansion cohorts of patients with advanced pancreatic cancer and non-small cell lung cancer. In parallel with the monotherapy dose escalation, Verastem will evaluate VS-7375 in combination with cetuximab in advanced solid tumors. Subject to the results of the Phase 1 dose escalation combination of VS-7375 and cetuximab, Verastem plans to initiate a combination expansion cohort in colorectal cancer.

"We are excited that the first patient has initiated treatment with VS-7375 in the U.S. We believe we can leverage VS-7375’s dual inhibition of both the ON/OFF states to improve on the efficacy seen to date with other KRAS G12D-selective agents. With the trial underway, we aim to accelerate the program’s development given the lack of FDA-approved, KRAS G12D-targeted treatments available to patients with KRAS G12D cancers," said John Hayslip, M.D., chief medical officer of Verastem Oncology. "We are strongly encouraged by the anti-tumor activity seen in the updated Phase 1 data presented at the ASCO (Free ASCO Whitepaper) Annual Meeting from our partner GenFleet Therapeutics’ trial in China. We are advancing VS-7375 in the U.S. to target KRAS G12D mutant advanced solid tumors in areas of significant unmet need, such as pancreatic, colorectal, and lung cancers."

About KRAS G12D

KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. The KRAS G12D mutation occurs most commonly in pancreatic (37%), colorectal (12.5%), endometrial (8%), and non-small cell lung (5%) cancers. Currently, no therapies are approved by the U.S. Food and Drug Administration (FDA) specifically targeting KRAS G12D mutations in cancer.

About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor

VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 is the lead program from the Verastem Oncology discovery, development, and commercialization collaboration with GenFleet Therapeutics. Verastem announced in April 2025 that the U.S. Investigational New Drug (IND) application for VS-7375 was cleared, and it initiated a Phase 1/2a clinical trial (NCT07020221), VS-7375-101, in May 2025. GenFleet’s IND for VS-7375 (known as GFH375 in China) was approved in China in June 2024, and initial safety and efficacy results from the Phase 1 portion of the study were announced at ASCO (Free ASCO Whitepaper) 2025. In February 2025, GenFleet announced that the first patient was dosed in the Phase 2 portion of the study.

On June 24, 2025 TuHURA Biosciences, Inc. (NASDAQ:HURA) ("TuHURA" or the "Company"), a Phase 3 immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy, reported the initiation of its Phase 3 accelerated approval trial of IFx-2.0, TuHURA’s lead innate immune agonist, in patients with advanced or metastatic Merkel cell carcinoma (MCC) (Press release, TuHURA Biosciences, JUN 24, 2025, View Source [SID1234654093]).

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IFx-2.0 is designed to overcome primary resistance to checkpoint inhibitors (CPIs), such as Keytruda (pembrolizumab), and has demonstrated systemic anti-tumor specific immune responses (an abscopal effect) when administered intratumorally into cutaneous, subcutaneous, or accessible nodal lesions in the Company’s Phase 1b trial of IFx-2.0 in patients with advanced or metastatic MCC. In the Phase 1b trial, patients with advanced or metastatic MCC who progressed on either pembrolizumab or avelumab (anti-PD(L)-1) therapy, received weekly administration of IFx-2.0 for up to three doses followed by rechallenge with anti-PD(L)-1 therapy. Results demonstrated an overall response rate of 63% (2 CR, 5 PR) with two responses lasting 23 and 33 months and five ongoing responses (6, 11, 13, 19 and 23 months) as of the last follow-up.

"The initiation of IFx-2.0’s Phase 3 accelerated approval trial is a significant milestone for TuHURA and for the 40% to 50% of patients with advanced or metastatic MCC who may not respond to first line treatment with Keytruda (pembrolizumab)," stated James Bianco, M.D., President and Chief Executive Officer of TuHURA Biosciences. "IFx-2.0’s potential ability to harness the power of a patient’s innate immune response leading to the activation and proliferation of tumor specific B cells and T cells represents a novel mechanism to overcome primary resistance to checkpoint inhibitors. As we start initiating study sites, we are grateful for the interest among investigators from leading cancer centers across the US in participating in this Phase 3 trial. We anticipate having more than half of the 22 participating sites open over the next 3-4 weeks, with the balance activated by the end of summer."

The Company’s Phase 3 accelerated approval trial of IFx-2.0, conducted under an SPA Agreement with the U.S. FDA, will evaluate IFx-2.0 as an adjunctive therapy administered weekly for three weeks concurrent with the approved dose and schedule for Keytruda compared to Keytruda plus placebo in the first line treatment for patients with advanced or metastatic MCC. Keytruda is currently approved in MCC under accelerated approval based on ORR. The pivotal trial for IFx-2.0 is expected to enroll 118 participants across approximately 22 to 25 U.S. sites. Trial participants will be randomized on a 1:1 basis and receive Keytruda in both arms, for up to two years, or until disease progression or Keytruda related toxicities. The primary endpoint for the trial is ORR with a key secondary endpoint of PFS. Other secondary endpoints are safety, duration of response, and overall survival. Accelerated approval is based on the successful achievement of the ORR primary endpoint. The key secondary endpoint of PFS, if successfully achieved without a detrimental effect on overall survival, could satisfy the requirement for regular approval without the requirement for a post approval confirmatory trial.

The initiation of the Phase 3 trial represents the achievement of a milestone for the third tranche of funding under the Company’s recently announced private placement, thereby trigging the purchase from the Company of an additional $2.23 million under the private placement financing.

On June 24, 2025 Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company advancing innovative cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Priority Review for its supplemental New Drug Application (sNDA) for Revuforj (revumenib) for the treatment of relapsed or refractory (R/R) mutant NPM1 (mNPM1) acute myeloid leukemia (AML) (Press release, Syndax, JUN 24, 2025, View Source [SID1234654092]). The sNDA is being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program and has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of October 25, 2025. RTOR allows for a more efficient review and close engagement between the sponsor and the FDA throughout the submission process.

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"We are pleased that the FDA has granted Priority Review to our sNDA in R/R mNPM1 AML, a filing which builds on the initial approval of Revuforj for R/R acute leukemia with a KMT2A translocation in 2024," said Michael A. Metzger, Chief Executive Officer. "Syndax is uniquely positioned to continue leading this exciting new therapeutic class with a first- and best-in-class menin inhibitor supported by compelling pivotal data across the broadest population of patients and a strong foundation already established among clinicians, payers, and other key stakeholders."

Revuforj is an oral, first-in-class menin inhibitor that was FDA approved in 2024 for the treatment of R/R acute leukemia with a KMT2A translocation in adult and pediatric patients one year and older. The sNDA, if approved, would expand the indication for Revuforj to include patients with R/R AML who have an NPM1 mutation, the most common genetic alteration in AML. The sNDA is supported by positive pivotal data from the AUGMENT-101 trial of revumenib in patients with R/R mNPM1 AML. Results from this population were published in the journal Blood in May 2025 and presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress Meeting in June 2025.

About Mutant NPM1 (mNPM1) Acute Myeloid Leukemia (AML)

Mutations in the NPM1 gene are the most common genetic alteration observed in adults with AML, occurring in approximately 30% of cases. Mutations in this gene play a critical role in the development of mutant NPM1 (mNPM1) AML, an aggressive blood cancer associated with high rates of relapse. Patients with relapsed or refractory mNPM1 AML have a poor prognosis and critical unmet need. Similar to KMT2A-rearranged acute leukemia, mNPM1 AML is highly dependent on the menin-KMT2A interaction and disruption of this interaction has been shown to lead to downregulation of certain leukemogenic genes. mNPM1 AML is routinely diagnosed through currently available screening techniques. There are currently no approved therapies that selectively target the underlying disease mechanisms driving mNPM1 AML.

About Revuforj (revumenib)

Revuforj (revumenib) is an oral, first-in-class, selective menin inhibitor that is FDA approved for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older.

The FDA has granted Priority Review to Syndax’s supplemental New Drug Application (sNDA) seeking the approval of revumenib for the treatment of R/R mNPM1 AML. The sNDA is being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program, which allows for a more efficient review and close engagement between the sponsor and FDA. The sNDA is supported by positive pivotal data from the AUGMENT-101 trial of revumenib in patients with R/R mNPM1 AML. Results from this population were published in the journal Blood and presented at the 2025 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress Meeting.

Additionally, multiple trials of revumenib in combination with standard-of-care agents in mNPM1 AML or KMT2A-rearranged acute leukemia are ongoing or planned across the treatment landscape, including in newly diagnosed patients.

Revumenib was previously granted Orphan Drug Designation for the treatment of AML, ALL and acute leukemias of ambiguous lineage (ALAL) by the U.S. FDA and for the treatment of AML by the European Commission. The U.S. FDA also granted Fast Track designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation and Breakthrough Therapy Designation for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, has occurred with Revuforj. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation syndrome: Revuforj can cause fatal or life-threatening differentiation syndrome (DS). Symptoms of DS, including those seen in patients treated with Revuforj, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, and/or hypotension. In clinical trials, DS occurred in 39 (29%) of 135 patients treated with Revuforj. DS was Grade 3 or 4 in 13% of patients and fatal in one. The median time to onset was 10 days (range 3-41 days). Some patients experienced more than 1 DS event. Treatment interruption was required for 7% of patients, and treatment was withdrawn for 1%.

Reduce the white blood cell count to less than 25 Gi/L prior to starting Revuforj. If DS is suspected, immediately initiate treatment with systemic corticosteroids (e.g., dexamethasone 10-mg IV every 12 hours in adults or dexamethasone 0.25-mg/kg/dose IV every 12 hours in pediatric patients weighing less than 40 kg) for a minimum of 3 days and until resolution of signs and symptoms. Institute supportive measures and hemodynamic monitoring until improvement. Interrupt Revuforj if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if DS recurs after tapering corticosteroids.

QTc interval prolongation: In the clinical trials, QTc interval prolongation was reported as an adverse reaction in 39 (29%) of 135 patients treated with Revuforj. QTc interval prolongation was Grade 3 in 12% of patients. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 8%, and the increase from baseline QTcF was greater than 60 msec in 18%. Revuforj dose reduction was required for 5% of patients due to QTc interval prolongation. QTc prolongation occurred in 16% of the 31 patients less than 17 years old, 33% of the 88 patients 17 years to less than 65 years old, and in 50% of the 16 patients 65 years or older.

Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to treatment with Revuforj. Perform an electrocardiogram (ECG) prior to initiation of Revuforj, and do not initiate Revuforj in patients with QTcF >450 msec. Perform an ECG at least once weekly for the first 4 weeks and at least monthly thereafter. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation.

Interrupt Revuforj if QTcF increases >480 msec and <500 msec, and restart Revuforj at the same dose twice daily after the QTcF interval returns to ≤480 msec
Interrupt Revuforj if QTcF increases >500 msec or by >60 msec from baseline, and restart Revuforj twice daily at the lower-dose level after the QTcF interval returns to ≤480 msec
Permanently discontinue Revuforj in patients with ventricular arrhythmias and in those who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.
Embryo-fetal toxicity: Revuforj can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Revuforj and for 4 months after the last dose of Revuforj.

ADVERSE REACTIONS
Fatal adverse reactions occurred in 4 (3%) patients who received Revuforj, including 2 with differentiation syndrome, 1 with hemorrhage, and 1 with sudden death.

Serious adverse reactions were reported in 99 (73%) patients. The most frequent serious adverse reactions (≥5%) were infection (24%), febrile neutropenia (19%), bacterial infection (17%), differentiation syndrome (12%), hemorrhage (9%), and thrombosis (5%).

The most common adverse reactions (≥20%) including laboratory abnormalities, were hemorrhage (53%), nausea (51%), phosphate increased (50%), musculoskeletal pain (42%), infection (41%), aspartate aminotransferase increased (37%), febrile neutropenia (35%), alanine aminotransferase increased (33%), parathyroid hormone intact increased (33%), bacterial infection (31%), diarrhea (30%), differentiation syndrome (29%), electrocardiogram QT prolonged (29%), phosphate decreased (25%), triglycerides increased (25%), potassium decreased (24%), decreased appetite (24%), constipation (23%), edema (23%), viral infection (23%), fatigue (22%), and alkaline phosphatase increased (21%).

DRUG INTERACTIONS
Drug interactions can occur when Revuforj is concomitantly used with:

Strong CYP3A4 inhibitors: reduce Revuforj dose
Strong or moderate CYP3A4 inducers: avoid concomitant use with Revuforj
QTc-prolonging drugs: avoid concomitant use with Revuforj. If concomitant use is unavoidable, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold Revuforj if the QTc interval is >480 msec. Restart Revuforj after the QTc interval returns to ≤480 msec.
SPECIFIC POPULATIONS
Lactation: advise lactating women not to breastfeed during treatment with Revuforj and for 1 week after the last dose.

Pregnancy and testing: Revuforj can cause fetal harm when administered to a pregnant woman. Verify pregnancy status in females of reproductive potential within 7 days prior to initiating Revuforj.

Pediatric: monitor bone growth and development in pediatric patients.

Geriatric: compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older.

Infertility: based on findings in animals, Revuforj may impair fertility. The effects on fertility were reversible.

To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals at 1-888-539-3REV or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see Full Prescribing Information, including BOXED WARNING.

About the Real-Time Oncology Review (RTOR) Program

RTOR provides a more efficient review process for oncology drugs to ensure that safe and effective treatments are available to patients as early as possible, while improving review quality and engaging in early iterative communication with the applicant. Specifically, it allows for close engagement between the sponsor and the FDA throughout the submission process and it enables the FDA to review individual sections of modules of a drug application rather than requiring the submission of complete modules or a complete application prior to initiating review. Additional information about RTOR can be found at: View Source

On June 24, 2025 Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, reported that it has partnered with Royalty Pharma on $2 billion in flexible funding to support Revolution Medicines’ independent global development and commercialization strategy and operations (Press release, Revolution Medicines, JUN 24, 2025, View Source [SID1234654091]). Revolution Medicines retains full strategic and executional control of product development and commercialization for its portfolio of RAS(ON) inhibitors in the US and internationally, enabling the company to leverage its assets, capabilities and momentum toward establishing new global standards of care and creating value for shareholders.

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"Today’s announcement represents a major boost to our bold vision on behalf of patients with RAS-addicted cancers," said Mark A. Goldsmith M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "This funding agreement significantly increases the financial resources we can deploy while preserving optionality as we scale our operations to create the industry-leading global targeted medicines franchise for patients with RAS-addicted cancers based on our highly differentiated RAS(ON) inhibitor portfolio."

"We are excited to announce today a groundbreaking partnership that provides Revolution Medicines with up to $2 billion of long-term capital through a customized funding solution that facilitates the expansive development and global commercialization of its leading RAS(ON) inhibitor portfolio," said Pablo Legorreta, founder and chief executive officer of Royalty Pharma. "This partnership exemplifies a new funding paradigm for highly innovative biotech companies. In contrast to a conventional pharma partnership, this large scale and flexible funding agreement enables Revolution Medicines to retain control of the clinical development of daraxonrasib, as well as the ability to capture significant value creation that would result from the successful clinical development and commercialization of its pipeline."

Transaction overview

The funding agreement provides for $2 billion in committed capital comprised of up to $1.25 billion in synthetic royalty monetization on sales of daraxonrasib, the company’s RAS(ON) multi-selective inhibitor, and up to $750 million in corporate debt. The agreement provides significant flexibility to Revolution Medicines with $1.25 billion of the total funding reserved as optional to the company at its discretion, subject to the achievement of specific milestones.

Synthetic royalty details

Royalty Pharma will provide up to $1.25 billion in exchange for tiered royalties for a term of 15 years on worldwide annual net sales of daraxonrasib; the royalties decrease based on sales and for sales above $8 billion the royalty rate is zero.
The $1.25 billion synthetic royalty funding is divided into five tranches of $250 million.
The first two $250 million tranches, totaling $500 million, are payable prior to daraxonrasib’s approval by the FDA and royalty obligations begin only after daraxonrasib approval. Revolution Medicines received the first $250 million tranche at closing and the second $250 million tranche is due to the company upon a positive data readout from the company’s RASolute 302 study, a global Phase 3 trial in patients with previously treated pancreatic ductal adenocarcinoma (PDAC).
The royalty rates on annual net sales for these two tranches are 4.55% on the first $2 billion, 2.50% on $2 billion to $4 billion, 1.00% on $4 billion to $8 billion and zero above $8 billion.
At annual net sales of $8 billion, the effective blended royalty rate for these tranches would be 2.26% and this rate progressively decreases as net sales increase above $8 billion.
The subsequent three equal tranches, totaling $750 million, are post-approval tranches that can be drawn at the company’s discretion after certain milestones are achieved.
In a scenario where the company draws the entire $1.25 billion:
The royalty rates for all five tranches on annual net sales are 7.80% on the first $2 billion, 4.55% on $2 billion to $4 billion, 2.40% on $4 billion to $8 billion and zero above $8 billion.
At annual net sales of $8 billion, the effective blended royalty rate would be 4.29% and this rate progressively decreases as net sales increase above $8 billion.
The potential exists for overlapping indication labels across certain assets within the company’s pipeline. If zoldonrasib, the company’s RAS(ON) G12D-selective inhibitor, were approved in the same indication as daraxonrasib, zoldonrasib sales would be included in the calculation of total net sales that are subject to the royalty schedule noted above. If zoldonrasib is approved solely for indications outside of daraxonrasib indications, zoldonrasib sales would not be subject to any royalties under the royalty agreement.
Debt details

The debt facility is an up to $750 million senior secured term loan consisting of three $250 million tranches linked to commercialization of daraxonrasib.
The company would receive the first debt tranche of $250 million following first FDA approval of daraxonrasib for the treatment of metastatic PDAC, if this occurs by January 1, 2028. Debt tranches two and three are optional at the company’s discretion and will be available to the company based on achievement of annual net sales milestones for daraxonrasib.
The term loan is an interest-only facility, with principal due at the earlier of (i) 6 years after the first tranche is funded and (ii) December 31, 2032. The interest rate is calculated based on the 3-month Standard Overnight Financing Rate (SOFR) plus 5.75%, with a SOFR floor of 3.50%.
Further details on this transaction can be found in the Current Report on Form 8-K filed by the company today with the Securities and Exchange Commission.

Cash runway update

As a result of entering into this funding agreement with Royalty Pharma, the company is removing its cash runway end date guidance.

Investor webcast

Revolution Medicines management will host an investor webcast today, June 24, at 8:00 a.m. ET (5:00 a.m. PT) to discuss this transaction. To participate in the live webcast, participants may register at View Source A live webcast of the call will be available on the Investors section of Revolution Medicines’ website at View Source Following the live webcast, a replay will be available on the company’s website for at least 14 days.

Advisors
TD Securities acted as financial advisor and Latham & Watkins acted as legal advisor to Revolution Medicines. Goodwin Procter and Maiwald acted as legal advisors to Royalty Pharma.