The Bottom Line

• NXP900 Shows Strong Synergy with ALK Inhibitors in ALK resistant NSCLC Cells: According to the recent presentations, NXP900 has shown synergy with ALK inhibitors, by strongly inhibiting ALK fusion-positive NSCLC cells that are resistant to treatment with single agent ALK inhibitors. This could extend the effectiveness of existing ALK treatments by targeting a well-established, resistance-inducing bypass mechanism.
• Industry Comparable: Similar players in the field of NSCLC like Nuvalent (NASDAQ: NUVL) and Summit Therapeutics (NASDAQ: SMMT) have seen strong growth following their clinical results in NSCLC. Nuvectis currently holds a valuation of approximately $150 million, and positive data down the road could be significant for the future of Nuvectis.
• Upcoming NXP800 Data: Anticipation is growing for upcoming data from NXP800 in platinum resistant, ARID1a mutated ovarian cancer, with many watching closely to see, beyond tumor shrinking activity, if thrombocytopenia, a previously observed side effect, can be effectively managed — a major factor for the drug’s continued development.

LONDON / Oct 28, 2024 / Business Wire / Nuvectis Pharma (NASDAQ: NVCT) is gaining momentum following recent presentations at the AACR-NCI-EORTC Symposium, where its SRC/YES1 inhibitor NXP900 demonstrated strong synergy with ALK inhibitors in NSCLC cells that despite being driven by ALK fusions, are resistant to treatment with the market leading ALK Inhibitors, alectinib (marketed by Roche) and lorlatinib (marketed by Pfizer). Meanwhile, NXP800, the company's GCN2 activator, is progressing in a Phase 1b trial targeting platinum resistant, ARID1a-mutated ovarian cancer, with a data update expected soon. This pipeline of innovative candidates has positioned Nuvectis at the forefront of precision oncology, and the market appears to be starting to take more notice as the company approaches important clinical milestones. Please refer to the disclaimers and disclosures also linked at the end of the report which it is subject to. Nothing contained herein is intended to serve as financial or investment advice.

NXP900 and the SRC/YES1 Kinase Advantage

NXP900, currently undergoing a Phase 1a dose-escalation trial, employs a novel approach to tackling cancer resistance by targeting SRC/YES1. In NSCLC and other malignancies, SRC and YES1 are key players in bypass-Induced acquired resistance. This distinguishes NXP900 from kinase Inhibitors that target the main driver of the cancer, such as ALK or EGFR inhibitors, by targeting the mechanism that the cancer utilizes to induce treatment resistance outside of the main pathway. In such situations, while the ALK/EGFR inhibitors can still effectively inhibit these targets, they fail to maintain a clinical response due to the bypass-Induced acquired resistance.

The data presented at the AACR-NCI-EORTC Symposium underscores NXP900’s impact on NSCLC cells - By inhibiting SRC/YES1 kinases, NXP900 directly targets the bypass-Induced acquired resistance mechanisms that often lead to disease progression. The data shows that NXP900 enhances the efficacy of the market leading ALK inhibitors, lorlatinib and alectinib in previously ALK-sensitive cell lines that became resistant to treatment. This synergy positions NXP900 as a frontrunner candidate for combination therapy to extend the effectiveness of ALK inhibitors.

Could Nuvectis Follow a Similar Path to Nuvalent (NASDAQ: NUVL)?

Nuvalent (NASDAQ: NUVL), a key emerging player in the ALK inhibitor space, offers an interesting comparison for understanding Nuvectis’ positioning. Nuvalent’s lead programs, NVL-655 and zidesamtinib, target ALK and ROS1 pathways in NSCLC and have shown promise in heavily pre-treated patients, including those with brain metastases. While Nuvalent’s drugs are still in Phase 2, the company garners a market cap of approximately $6.6 billion—an indicator of investor confidence in resistance-targeting therapies.

In contrast, Nuvectis’ NXP900, which addresses both ALK and EGFR mutations and targets SRC/YES1-driven cancers, has a much broader potential application. With a current market cap of approximately $150 million even after rising in recent weeks, many are arguing that Nuvectis appears undervalued relative to its peers and could follow a similar trajectory to Nuvalent if it demonstrates clinical proof of concept.

Moreover, Summit Therapeutics’ recent success with ivonescimab in another subset of NSCLC reflects a broader trend in oncology, where therapies addressing resistance mechanisms often yield dramatic valuation growth. Ivonescimab’s Phase 3 success drove Summit’s market cap to nearly $19 billion (currently at $15B), illustrating the high market demand for treatments that prolong patient response in resistant cancers. As Nuvectis advances NXP900, it could similarly capitalize on this momentum, with the potential for significant value appreciation if clinical data continues to show promise.

Building Momentum as Anticipation Grows for Upcoming NXP800 Data

Beyond NXP900, Nuvectis is also preparing for an important data readout for NXP800, in platinum resistant, ARID1a-mutated ovarian cancer. NXP800, which has received FDA Orphan Drug and Fast Track designations, has shown encouraging preclinical efficacy in both platinum-sensitive and resistant ARID1a mutated ovarian cancer models, positioning it as a potential breakthrough in a cancer subtype with limited treatment options.

A key factor many will likely be watching with NXP800’s upcoming data is the management of thrombocytopenia, a previously observed side effect that initially raised concerns about the drug's viability. If the upcoming data suggests that thrombocytopenia can be effectively managed, it could clear a major hurdle in the ongoing development program. Positive results could serve as an Important milestone for Nuvectis as it also advances NXP900— which caters to a substantially larger market opportunity.

Leadership and Insider Confidence

Nuvectis’ leadership team, comprised of Ron Bentsur, Shay Shemesh, and Enrique Poradosu, has demonstrated strong confidence in the company’s future by consistently increasing their stakes. Together, they own approximately 35% of Nuvectis, aligning their interests closely with shareholders and underscoring their commitment to the company's success. Collectively, Nuvectis' co-founders bring over 50 years of biotech experience and a proven track record of performance, including spearheading the approval of three drugs, two of which are for unmet medical needs in oncology.

Alongside the regulatory success, the previous companies led by the co-founders experienced significant value creation. Ron Bentsur, Nuvectis' CEO, previously served as CEO of UroGen Pharma and Keryx Biopharmaceuticals, Bentsur led both companies through transformative growth. At UroGen, he led the company’s IPO in 2017, resulting in a stock price surge from $13 to $70 per share within a year. At Keryx, his strategic leadership saw the stock rise from $0.25 to $20 per share over two years.

Looking Ahead

It seems that Nuvectis Pharma is positioned at an exciting juncture. With NXP900's potential in NSCLC and anticipated data for NXP800 coming up soon, the company could emerge as a key player in precision oncology. As clinical development advances for both NXP900 and NXP800, Nuvectis has the potential to achieve substantial growth, potentially similar to peers like Nuvalent and Summit. While the nature of early-stage biotech remains high-risk, Nuvectis’ strategic direction, robust insider confidence and experience, and innovative approach to cancer resistance management make it a promising prospect as it approaches these critical milestones.

Nuvectis Pharma (NASDAQ: NVCT) continues to make strides in precision oncology, gaining momentum following presentations last week at the AACR-NCI-EORTC Symposium where its drug candidate NXP900 demonstrated strong synergy with ALK inhibitors in non-small cell lung cancer (NSCLC) cells that despite being driven by ALK fusions, are resistant to treatment with the market leading ALK Inhibitors, alectinib and lorlatinib, showcasing NXP900's potential to address resistance mechanisms in NSCLC. Also, with the growing anticipation of the data update from NXP800 expected soon from the Phase 1b study in platinum resistant, ARID1a-mutated ovarian cancer, Nuvectis is positioning itself at the forefront of precision oncology and cancer resistance management, drawing comparisons to notable industry players such as Summit Therapeutics ($15B) and Nuvalent ($6.6B).