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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

On June 24, 2025 Priothera, a late-stage biopharma company pioneering the development of mocravimod, a novel oral sphingosine 1 phosphate (S1P) receptor modulator, to treat hematologic malignancies, reported that it has been awarded nearly €1.7 million in non-dilutive funding through the i-Nov innovation competition (Press release, Priothera, JUN 24, 2025, View Source [SID1234654090]). Part of the France 2030 initiative, i-Nov is a flagship French government program operated by Bpifrance to support breakthrough innovation from high-potential French companies across strategic sectors. The funding will support Priothera’s clinical programme to evaluate whether adding mocravimod to commercial CAR-T cell therapies could improve patient outcomes.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CAR-T cell therapies represent a novel and promising modality for the treatment of hematological malignancies. They have demonstrated the potential for remarkable clinical responses and durable disease control in patients with acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma and multiple myeloma. However, their use is still associated with significant challenges, as 40-60% of patients treated with CAR-T cells experience high-grade toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), a form of severe neurological toxicity.

Mocravimod is a novel, oral S1P receptor modulator with a unique dual mechanism of action that has the potential to enhance the effectiveness of CAR-T cell therapy by:

Reducing the incidence and severity of CRS and ICANS, and
Improving response rates and durability of treatment

"We are honoured to receive this i-Nov funding from Bpifrance, which underscores the innovation and therapeutic potential of mocravimod beyond allo-HCT," said Florent Gros, Co-Founder and CEO of Priothera. "With its unique immunomodulatory properties, mocravimod is well-positioned to become a key component in the next generation of cell therapy regimens. The MOCART trial represents an exciting expansion of our clinical development into CAR-T therapy, building on our deep expertise in allo-HCT and momentum from our ongoing global Phase 3 MO-TRANS trial in acute myeloid leukemia."
Priothera continues to advance mocravimod in the MO-TRANS global Phase 3 study for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The company remains focused on unlocking the full therapeutic potential of S1P receptor modulation across multiple settings in blood cancers.

About mocravimod
Mocravimod (KRP203) is a synthetic S1P receptor modulator being developed for the adjunctive and maintenance treatment of AML to enhance the curative potential of allo-HCT. Mocravimod’s dual mechanism of action preserves the graft-versus-leukemia (GvL) effect, critical for eliminating cancer cells while reducing the risk of graft-versus-host disease (GvHD), a major complication following allo-HCT. This novel treatment approach – mocravimod being the only S1P receptor modulator in development to treat blood cancers – tackles a high unmet medical need and aims to improve treatment outcomes and patients’ quality of life.

On June 24, 2025 Philogen S.p.A (BIT: PHIL) ("Philogen") reported the decision to voluntarily withdraw the application for marketing authorization to the European Medicines Agency (EMA) for Nidlegy, a biological investigational medicinal product which is intended to be used for the neoadjuvant treatment of adult patients with locally advanced fully resectable melanoma (Press release, Philogen, JUN 24, 2025, View Source [SID1234654089]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Marketing Authorization Application (MAA) for Nidlegy submitted in June 2024 was supported by data from PIVOTAL (NCT02938299), a randomized Phase 3 study in 256 patients with locally advanced fully resectable melanoma, in which Nidlegy reduced the risk of relapse or death by 41% compared to the control arm (Hauschild et al. Journal of Clinical Oncology 2024, 43; Kähler et al Annals of Oncology, 2025, manuscript accepted). The safety profile of Nidlegy was characterized mostly by low-grade, local adverse events.

The company’s decision to withdraw the MAA was due to the timing of the availability of Chemistry Manufacturing and Controls (CMC) and additional clinical data to better characterize the benefit:risk profile in patients with locally advanced resectable melanoma. Provision of the CMC and clinical data were unlikely to be completed within the current allowed timeframe.

Philogen remains confident in the favorable benefit-risk profile of Nidlegy, underscored by its clinically meaningful efficacy and tolerable safety profile in both melanoma (Hauschild et al. Journal of Clinical Oncology 2024, 43, Kähler et al. Annals of Oncology, 2025, manuscript accepted) and in non-melanoma skin cancers (Flatz et al. JEADV 2025, 39, e147). Until now, Nidlegy has been given to more than 450 patients with different types of skin cancer.

The company continues to closely interact with the EMA and with the medical community, with the goal of making Nidlegy available to both melanoma and non-melanoma skin cancer patients as soon as possible.

Prof. Dr. Dario Neri, CEO and CSO of Philogen, commented: "After careful consideration of the feedback and ongoing dialogue with EMA, we have decided to withdraw the MAA for Nidlegy and resubmit an updated application, in view of the potential of the product in melanoma and beyond. We are working closely together with EMA to address their requests in preparation of the forthcoming resubmission of the MAA."

On June 24, 2025 Nuvalent, Inc. (the "Company") reported positive pivotal data for zidesamtinib, a novel ROS1-selective inhibitor, in tyrosine kinase inhibitor ("TKI") pre-treated patients with advanced ROS1-positive non-small cell lung cancer ("NSCLC") from the global ARROS-1 Phase 1/2 clinical trial (Press release, Nuvalent, JUN 24, 2025, View Source [SID1234654087]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In addition, Nuvalent announced progress on the front-line development strategies for its parallel lead programs in ROS1-positive and ALK-positive NSCLC, including:

•
The first report of preliminary data from the Phase 2 TKI-naïve cohort in its ARROS-1 clinical trial, in which global enrollment is ongoing; and,
•
The advancement of clinical startup activities to support the global initiation of the ALKAZAR Phase 3, randomized, controlled trial. The trial is designed to evaluate neladalkib, a novel ALK-selective inhibitor, versus alectinib, a front-line standard of care, for the treatment of patients with TKI-naïve ALK-positive NSCLC, and the Company expects to begin enrollment early in the second half of 2025.
The Company completed a pre-New Drug Application ("NDA") meeting with the U.S. Food and Drug Administration ("FDA") and aligned on its plans to move forward with an NDA submission seeking an indication for the treatment of zidesamtinib for TKI pre-treated patients with locally advanced or metastatic ROS1-positive NSCLC. The FDA agreed to accept the NDA for participation in the Real-Time Oncology Review ("RTOR") pilot program, which facilitates earlier submission of topline data to support an earlier start to the FDA’s evaluation of the application. The Company plans to initiate a rolling NDA submission in July 2025 with completion targeted for the third quarter of 2025, and continues to engage with the FDA on potential opportunities for line-agnostic expansion.

Summary of Pivotal Data

Zidesamtinib is being evaluated in ARROS-1, a first-in-human Phase 1/2 clinical trial for patients with advanced ROS1-positive NSCLC and other solid tumors. The recommended phase 2 dose ("RP2D") for zidesamtinib of 100 mg once daily ("QD") was determined during the Phase 1 dose-escalation portion of the trial. The ongoing global, single arm, multi-cohort, open label Phase 2 portion is designed to evaluate zidesamtinib at the RP2D with registrational intent for both TKI-naïve and TKI pre-treated patients with advanced ROS1-positive NSCLC.

In this pivotal dataset for the TKI pre-treated ROS1-positive NSCLC population, data are pooled across Phase 1 and 2 and reported for the primary objective of objective response rate ("ORR", RECIST 1.1) by blinded independent central review ("BICR"). Key secondary objectives include duration of response ("DOR"), intracranial ORR ("IC-ORR"), and safety.

As of the data cut-off date of March 21, 2025, 514 patients with ROS1-positive solid tumors had received zidesamtinib at any starting dose across the Phase 1 and Phase 2 portions of the ARROS-1 clinical trial. Of these, 432 patients with advanced ROS1-positive NSCLC were treated with zidesamtinib at the RP2D.

Efficacy Analysis in TKI Pre-treated Advanced ROS1-positive NSCLC

The primary analysis population consisted of 117 TKI pre-treated patients with advanced ROS1-positive NSCLC with measurable disease who received zidesamtinib at the RP2D by May 31, 2024 with DOR follow-up of at least 6 months available for nearly all responders.

The primary analysis population was distinct from the ROS1 TKI pre-treated populations that have been reported for the current available and investigational ROS1 TKIs:

Patients received a median of 2 prior lines of therapy (range, 1 – 11) and 53% had received prior chemotherapy.

•
47% of patients received crizotinib or entrectinib, the most commonly used front-line TKIs, as their only ROS1 TKI ± prior chemotherapy. Within this subset, 51% of patients received prior crizotinib and 49% of patients received prior entrectinib; 47% of patients received prior chemotherapy.
•
50% of patients had received 2 or more prior ROS1 TKIs ± prior chemotherapy, of which 93% had received prior lorlatinib, repotrectinib, or taletrectinib.
•
36% of patients had a secondary ROS1 resistance mutation, a key driver of disease progression.
•
49% of patients had active CNS disease by BICR, including cases of disease progression following treatment with the brain-penetrant TKIs lorlatinib, repotrectinib, and/or taletrectinib.
Activity was observed across subsets of TKI pre-treated patients, and durability of response was assessed as the probability of patients remaining in response for at least 6, 12 and 18 months by Kaplan-Meier estimate (Table 1). Median duration of response ("mDOR") continues to mature.

Table 1.

All TKI Pre-treated a

1 prior ROS1 TKI

(crizotinib or entrectinib)

± chemotherapy b

n

117

55

ORR, % (n/N)

(95% CI)

44% (51/117) c

(34, 53)

51% (28/55) d

(37, 65)

% DOR ≥ 6 months e

(95% CI)

84%

(71, 92)

93%

(74, 98)

% DOR ≥ 12 months e

(95% CI)

78%

(62, 88)

93%

(74, 98)

% DOR ≥ 18 months e

(95% CI)

62%

(28, 84)

93%

(74, 98)

G2032R mutation f

n

26

6

ORR, % (n/N)

(95% CI)

54% (14/26)

(33, 73)

83% (5/6)

(36, 100)

% DOR ≥ 6 months e

(95% CI)

79%

(47, 93)

80%

(20, 97)

% DOR ≥ 12 months e

(95% CI)

60%

(28, 81)

80%

(20, 97)

NE = not estimable.

a The median duration of follow-up was 11.1 months (range 0.2 – 25.6) and mDOR continue to mature. For responders, the emerging mDOR was 22.0 months (95% CI: 17.2, NE) overall and 17.2 months (95% CI: 3.7, NE) for the subset with G2032R.

b The median duration of follow-up was 11.8 months (range 1.2 – 25.6) and mDOR continue to mature. For responders, the emerging mDOR was 22.0 months (95% CI: 22.0, NE) overall and NE (95% CI: 1.9, NE) for the subset with G2032R.

c Includes responses observed in patients previously treated with at least 2 prior ROS1 TKIs ± chemotherapy (22/58, ORR = 38%), and in patients previously treated with repotrectinib (8/17, ORR = 47%) or taletrectinib (3/7, ORR = 43%).

d For patients receiving crizotinib only ± chemotherapy, ORR was 68% (19/28) with no progression events among responders. For patients receiving entrectinib only ± chemotherapy, ORR was 33% (9/27) with three progression events among responders.

e Estimated for responders by Kaplan-Meier analysis.

f ROS1 G2032R mutation identified in local or central testing of blood ("ctDNA") or tissue.

In patients that had measurable CNS lesions by BICR at baseline (n = 56), the IC-ORR was 48% with 20% (11/56) intracranial complete responses ("CR") and 2 unconfirmed partial responses ("PR"), and IC-DOR ≥ 12 months of 71% (95% CI: 46, 87).

•
In patients that had only received prior crizotinib, which has limited brain penetrance, ± chemotherapy (n = 13), the IC-ORR was 85% with 54% (7/13) intracranial CRs. There was only one CNS progression event among CNS responders.
•
Intracranial responses were also observed in patients previously treated with the brain-penetrant TKIs entrectinib, lorlatinib, repotrectinib or taletrectinib.
Safety Analyses in Advanced ROS1-positive NSCLC

Zidesamtinib demonstrated a well-tolerated safety profile consistent with its ROS1-selective, TRK-sparing design.

In the 432 patients with advanced ROS1-positive NSCLC treated at RP2D as of the data cut-off date, the median duration of exposure was 5 months (range, 0, 32). The most frequent treatment-emergent adverse events ("TEAEs") occurring in ≥ 15% of patients were peripheral edema (36%), constipation (17%), blood CPK increase (16%), fatigue (16%), and dyspnea (15%).

Dose reductions due to TEAEs occurred in 10% of patients and 2% of patients discontinued treatment due to TEAEs.

Preliminary Data for TKI-Naïve Patients with Advanced ROS1-positive NSCLC

Encouraging preliminary data were available for 35 TKI-naïve patients with advanced ROS1-positive NSCLC treated with zidesamtinib at RP2D as of August 31, 2024. Patients may have received up to one prior line of chemotherapy.

The preliminary ORR was 89% (31/35) and DOR ranged from 1.9+ to 13.9+ months with DOR ≥ 6 months and 12 months of 96% (95% CI: 76, 99). In 6 patients with measurable intracranial lesions, the IC-ORR was 83% (5/6) and the intracranial CR rate was 67% (4/6). The IC-DOR ranged from 4.6+ to 11.1+ months with no CNS progression among responders.

As of June 16, 2025, a total of 104 patients had been enrolled in the ongoing TKI-naïve cohort of the ARROS-1 trial.

On June 24, 2025 NUCLIDIUM AG a clinical-stage radiopharmaceutical company developing copper-based theranostics, reported positive data from the Phase 1 clinical trial evaluating the company’s novel PET imaging agent, 61Cu-NuriProTM (61Cu-NODAGA-PSMA I&T) in patients with metastatic prostate cancer (Press release, NUCLIDIUM, JUN 24, 2025, View Source [SID1234654086]). These data were presented on June 23 at the Society of Nuclear Medicine & Molecular Imaging (SNMMI) 2025 Annual Meeting in New Orleans by Dr. Gary Ulaner, MD, PhD, Director of Molecular Imaging and Therapy at Hoag Family Cancer Institute and Principal Investigator for the trial. Dr. Ulaner highlighted 61Cu-NuriPro’s favorable safety, dosimetry profile and imaging characteristics in Prostate Specific Membrane Antigen (PSMA)-positive prostate cancer patients.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Phase 1 trial conducted at Hoag Molecular Imaging and Therapy Clinic evaluated the safety, dosimetry and preliminary diagnostic efficacy of 61Cu-NuriProTM in patients with metastatic prostate cancer, and was compared to 18F-piflufolastat. 61Cu-NuriPro demonstrated a safety profile comparable to clinically established PSMA tracers with a favorable imaging performance. Notably, 61Cu-NuriPro PET visualized additional lesions in 50% of the patients which were not seen on the 18F-piflufolastat PET, with favorable tumor-to-background ratios. The number of detected lesions on the 61Cu-NuriPro PET increased up to 4 hours after administration, highlighting the diagnostic benefits of 61Cu’s 3.3-hour half-life and high positron yield.

"Accurate and reliable imaging remains essential in the management of prostate cancer. The Phase 1 results from 61Cu-NuriPro demonstrate not only a solid safety profile but also good imaging quality compared to standard-of-care," said Dr. Gary Ulaner, MD, PhD, Director of Molecular Imaging and Therapy at Hoag Memorial Hospital Presbyterian and Principal Investigator of the trial. "These early data suggest strong potential for improving diagnostic performance and patient outcomes."

Leila Jaafar, PhD, CEO and Co-Founder of NUCLIDIUM added "These results further validate our first-in-class copper theranostics platform and the clinical promise of 61Cu-NuriPro as a potential best-in-class diagnostic. We are dedicated to rapidly advancing our portfolio of copper-based theranostic agents for a broader range of cancers, with a focus on safety, sustainability, and scalability."

61Cu-NuriProTM (61Cu-NODAGA-PSMA I&T) is the diagnostic component of NUCLIDIUM’s PSMA-targeted NuriProTM program[2],[3],[4],[5],[6]. The company’s second diagnostic, 61Cu-TraceNET, targeting SSTR-positive tumors, is in a Phase 1/2a clinical trial in broncho-pulmonary, and gastroenterohepatic neuroendocrine tumors (BP- and GEP-NETs). The agent will be developed further for imaging in a subset of metastatic breast cancer patients. Clinical trials of two corresponding therapeutics, 67Cu-NuriPro and 67Cu-TraceNET, are expected to start enrollment in early 2026.