Positive Pooled Data from Nuvation Bio’s TRUST-I and TRUST-II Studies Highlight Taletrectinib’s Best-in-Class Potential for Patients with Advanced ROS1-positive NSCLC, Supporting Planned New Drug Application Submission in the Fourth Quarter of 2024

Rhea-AI Summary

Nuvation Bio (NYSE: NUVB) announced positive pooled data from TRUST-I and TRUST-II studies evaluating taletrectinib, a next-generation ROS1 TKI for advanced ROS1-positive NSCLC. Key findings include:

- 89% tumor shrinkage in TKI-naïve patients
- 56% tumor shrinkage in TKI-pretreated patients
- Median DOR of 44 months and PFS of 46 months in TKI-naïve patients
- Favorable safety profile with low neurologic TEAEs

Nuvation Bio plans to submit an NDA to the FDA in Q4 2024, aiming for a U.S. launch in 2025. The data support taletrectinib's potential as a best-in-class treatment for ROS1-positive NSCLC.

Positive

• 89% tumor shrinkage rate in TKI-naïve patients
• 56% tumor shrinkage rate in TKI-pretreated patients
• Median duration of response of 44 months in TKI-naïve patients
• Median progression-free survival of 46 months in TKI-naïve patients
• 77% intracranial tumor shrinkage in TKI-naïve patients with brain metastases
• 66% intracranial tumor shrinkage in TKI-pretreated patients with brain metastases
• Favorable safety profile with low incidence of neurologic TEAEs
• Low treatment discontinuation rate of 7% due to TEAEs

Negative

• 29% dose reduction rate due to TEAEs

Oncology Expert

The pooled data from TRUST-I and TRUST-II studies demonstrate taletrectinib's impressive efficacy in ROS1+ NSCLC patients. With a 89% tumor shrinkage rate in TKI-naïve patients and 56% in TKI-pretreated patients, these results are highly encouraging. The median DOR of 44 months and PFS of 46 months in TKI-naïve patients are particularly noteworthy, suggesting durable responses and long-term disease control. The drug's efficacy against brain metastases (77% intracranial cORR in TKI-naïve) addresses a critical unmet need in NSCLC treatment. Moreover, its activity against the G2032R mutation (62% cORR) indicates potential in overcoming resistance mechanisms. These results position taletrectinib as a promising option in the ROS1+ NSCLC treatment landscape.

Medical Research Analyst

Taletrectinib's safety profile is a key highlight of this data. The low incidence of neurologic TEAEs and treatment discontinuations (7%) suggest better tolerability compared to existing ROS1 inhibitors. While liver enzyme elevations were common, severe cases (≥ Grade 3) were relatively infrequent. The 29% dose reduction rate due to TEAEs indicates manageable toxicity. This favorable safety profile, combined with its efficacy, could potentially allow for longer treatment duration, contributing to improved outcomes. The data support taletrectinib's potential as a best-in-class ROS1 TKI, offering a balance of efficacy and tolerability that could significantly impact treatment strategies for ROS1+ NSCLC patients.

Financial Analyst

The positive pooled data significantly strengthen Nuvation Bio's position in the competitive oncology market. With plans to submit an NDA in Q4 2024 and potential U.S. launch in 2025, taletrectinib could become a major revenue driver for the company. The global NSCLC market, valued at $19.3 billion in 2023, is projected to grow substantially. While ROS1+ cases represent a niche (1-2% of NSCLC), taletrectinib's potential best-in-class profile could capture a significant market share. Investors should note the planned transition to a commercial-stage organization, which could impact financial metrics and valuation. However, the path to commercialization will require significant investment in marketing and distribution infrastructure. The stock may see increased interest as the NDA submission approaches, but investors should remain cautious of regulatory risks and potential competition in this space.

Tumors shrank in 89% of taletrectinib-treated patients with advanced ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC) who were tyrosine kinase inhibitor (TKI)-naïve and 56% of those who were TKI-pretreated in the study

Taletrectinib demonstrated durable responses and prolonged progression-free survival (PFS) with long-term follow up; median duration of response (DOR) and median PFS in TKI-naïve patients were 44 months and 46 months, respectively

Taletrectinib demonstrated a favorable safety and tolerability profile, including low incidence of neurologic treatment-emergent adverse events (TEAEs) and low rate of treatment discontinuation

Nuvation Bio plans to submit a New Drug Application (NDA) for taletrectinib to the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2024

NEW YORK--(BUSINESS WIRE)-- Nuvation Bio Inc. (NYSE: NUVB), a late clinical-stage, global biopharmaceutical company tackling some of the greatest unmet needs in oncology, today announced positive pooled data from the pivotal Phase 2 TRUST-I and TRUST-II studies evaluating taletrectinib, an investigational next-generation ROS1 TKI. The findings will be highlighted in a poster presentation on September 14, 2024, at the European Society of Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain.

Maurice Perol, M.D., TRUST-II study investigator and Head of Thoracic Oncology at Léon Bérard Cancer Center, commented on the results: “The unmet need for more effective and tolerable treatments for patients with advanced ROS1-positive NSCLC remains critical. The pooled analysis from the TRUST-I and TRUST-II studies reinforces taletrectinib’s potential to offer clinically meaningful advancements in efficacy combined with a favorable safety profile, including reported median duration of response of 44 months and progression-free survival of 46 months in patients who were TKI-naïve.”

“We are excited to present compelling pooled data from the TRUST-I and TRUST-II studies at ESMO, which highlight taletrectinib’s durable response, prolonged disease control, and favorable safety profile. We believe these results position taletrectinib as a potential best-in-class treatment option for people living with advanced ROS1-positive NSCLC,” said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. “These pivotal data will support our planned NDA submission in the fourth quarter of 2024 and, assuming regulatory approval, will enable us to launch taletrectinib in the U.S. in 2025. We are committed to making a positive impact on the lung cancer community and look forward to sharing updates as we continue toward becoming a commercial stage organization.”

Summary of Pivotal Pooled Data

The pooled efficacy and safety data from the TRUST-I and TRUST-II studies presented at ESMO are as of June 7, 2024; both studies remain ongoing. The ESMO data set includes 337 patients with advanced ROS1+ NSCLC who received 600mg of taletrectinib orally once daily in 21-day cycles.

The primary endpoint of these registrational studies is confirmed objective response rate (cORR) as assessed by an independent review committee (IRC). Key secondary endpoints include intracranial cORR, DOR, PFS, and safety.

Significant Tumor Shrinkage and Durability

The pooled efficacy analyses included 160 patients with advanced ROS1+ NSCLC who had not previously been treated with a ROS1 TKI (TKI-naïve) and 113 patients who had previously been treated with crizotinib or entrectinib (TKI-pretreated).

Among these two populations, 94% of patients had stage IV NSCLC. In addition, 20% of TKI-naïve and 37% of TKI-pretreated patients received prior chemotherapy, while 23% of TKI-naïve and 49% of TKI-pretreated patients had brain metastases at baseline.

The efficacy results, independently assessed by an IRC, showed:

In TKI-naïve patients (n=160):

• Tumors shrank in 89% of taletrectinib-treated patients (cORR).
• Measurable brain metastases shrank in 77% (13/17) of taletrectinib-treated patients (intracranial cORR).
• After median follow-up of 21 months, the median DOR and the median PFS were 44 months and 46 months, respectively.

In TKI-pretreated patients (n=113):

• Tumors shrank in 56% of taletrectinib-treated patients (cORR).
• Measurable brain metastases shrank in 66% (21/32) of taletrectinib-treated patients (intracranial cORR).
• Tumors shrank in 62% (8/13) of taletrectinib-treated patients with G2032R mutations (cORR).
• After median follow-up of 21 months, the median DOR and the median PFS were 17 months and 10 months, respectively.

Favorable and Consistent Safety Profile Across Studies

The pooled safety analysis included 337 patients with advanced ROS1+ NSCLC. The results demonstrated a favorable safety and tolerability profile, with a low incidence and a limited spectrum of neurologic TEAEs and a low rate of treatment discontinuation.

The most frequent TEAEs were increased aspartate aminotransferase (72%; 8% ≥ Grade 3), alanine aminotransferase (68%; 10% ≥ Grade 3), diarrhea (63%; 2% ≥ Grade 3), and nausea (47%; 2% ≥ Grade 3).

The incidence of neurologic TEAEs was low; the most common were dizziness (21%) and dysgeusia (15%), most of which were Grade 1. The rate of treatment discontinuation due to TEAEs was 7% and the rate of dose reduction due to TEAEs was 29%.

Data Presentation and Availability

The data in the ESMO poster from the Response Evaluable Population, which includes all patients with measurable disease who received at least one dose of taletrectinib as of June 7, 2024, form the primary efficacy analysis that will support Nuvation Bio’s planned NDA submission in the United States.

The data in the ESMO abstract represent clinical results from patients enrolled at least 14 months before the data cutoff of March 29, 2024.

The poster presentation (abstract #1289P) will take place on Saturday, September 14, 2024, at 12:00-1:00 p.m. CEST / 6:00-7:00 a.m. EDT, and is available on Nuvation Bio’s website at www.nuvationbio.com/publications.

About Taletrectinib

Taletrectinib is an oral, potent, central nervous system-active, selective, next-generation ROS1 inhibitor specifically designed for the treatment of patients with advanced ROS1+ NSCLC. Taletrectinib is being evaluated for the treatment of patients with advanced ROS1+ NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global study.

Taletrectinib has been granted Orphan Drug Designation by the U.S. FDA for the treatment of patients with ROS1+ NSCLC and other NSCLC indications, and Breakthrough Therapy Designations by both the U.S. FDA and China’s National Medical Products Administration (NMPA) for the treatment of patients with advanced or metastatic ROS1+ NSCLC. Based on results of the TRUST-I clinical study, China’s NMPA has accepted and granted Priority Review Designations to New Drug Applications for taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC who either have or have not previously been treated with ROS1 TKIs.

In 2021, AnHeart Therapeutics Ltd., a Nuvation Bio company, entered into an exclusive license agreement with Innovent Biologics, Inc. for the co-development and commercialization of taletrectinib in Greater China, including mainland China, Hong Kong, Macau, and Taiwan.

About ROS1+ NSCLC

Each year, more than one million people globally are diagnosed with NSCLC, the most common form of lung cancer. It is estimated that approximately 2% of people with NSCLC have ROS1+ disease. Up to 35% of people newly diagnosed with metastatic ROS1+ NSCLC have tumors that spread to their brain, increasing up to 55% for those whose cancer has progressed following initial treatment. Despite recent progress for people with ROS1+ NSCLC, there remains a need for more effective and tolerable treatment options.

About Nuvation Bio

Nuvation Bio is a late clinical-stage, global biopharmaceutical company tackling some of the greatest unmet needs in oncology by developing differentiated and novel product candidates. Nuvation Bio’s portfolio of development candidates includes taletrectinib (ROS1), safusidenib (mIDH1), NUV-1511 (DDC), and NUV-868 (BET). Nuvation Bio was founded in 2018 by biopharma industry veteran David Hung, M.D., who previously founded Medivation, Inc., which brought to patients one of the world’s leading prostate cancer medicines. Nuvation Bio has offices in New York, San Francisco, Boston, and Shanghai. For more information, please visit www.nuvationbio.com and https://www.linkedin.com/company/nuvationbio/.

Forward Looking Statements

Certain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements are sometimes accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, our expectations regarding a U.S. NDA and timing of its submission, our expectations of establishing a commercial organization, the potential for taletrectinib to become a new therapeutic option for ROS1+ NSCLC, and taletrectinib’s best-in-class therapeutic potential. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of the management team of Nuvation Bio and are not predictions of actual performance. These forward-looking statements are subject to a number of risks and uncertainties that may cause actual results to differ from those anticipated by the forward-looking statements, including but not limited to the challenges associated with conducting drug discovery and initiating or conducting clinical trials due to, among other things, difficulties or delays in the regulatory process, enrolling subjects or manufacturing or acquiring necessary products; the emergence or worsening of adverse events or other undesirable side effects; risks associated with preliminary and interim data, which may not be representative of more mature data; competitive developments; and establishing commercial capabilities. Risks and uncertainties facing Nuvation Bio are described more fully in its Form 10-Q filed with the SEC on August 5, 2024, under the heading “Risk Factors,” and other documents that Nuvation Bio has filed or will file with the SEC. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this press release. Nuvation Bio disclaims any obligation or undertaking to update, supplement or revise any forward-looking statements contained in this press release.

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Source: Nuvation Bio Inc.

FAQ

What is the efficacy of taletrectinib in TKI-naïve ROS1-positive NSCLC patients?

Taletrectinib showed an 89% tumor shrinkage rate (cORR) in TKI-naïve ROS1-positive NSCLC patients, with a median duration of response of 44 months and progression-free survival of 46 months.

How effective is taletrectinib for ROS1-positive NSCLC patients with brain metastases?

Taletrectinib demonstrated high intracranial efficacy, with 77% of TKI-naïve and 66% of TKI-pretreated patients with measurable brain metastases experiencing tumor shrinkage.

What is the safety profile of taletrectinib for ROS1-positive NSCLC?

Taletrectinib showed a favorable safety profile with a low incidence of neurologic TEAEs. The most common side effects were increased liver enzymes, diarrhea, and nausea. The treatment discontinuation rate was low at 7%.

When does Nuvation Bio (NUVB) plan to submit an NDA for taletrectinib?

Nuvation Bio plans to submit a New Drug Application (NDA) for taletrectinib to the FDA in the fourth quarter of 2024, with a potential U.S. launch in 2025.

How many patients were included in the pooled analysis of taletrectinib for ROS1-positive NSCLC?

The pooled analysis included 337 patients with advanced ROS1-positive NSCLC who received 600mg of taletrectinib orally once daily in 21-day cycles.