ISA Pharma Publishes Phase 2 Study Data in Major Peer-reviewed Journal

Synergy between Synthetic Long Peptides (SLP^®) immunotherapeutics and standard chemotherapy in late stage cancer including meaningful survival improvements in SLP immune responders

LEIDEN, Netherlands, March 19, 2020 /PRNewswire/ -- ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company, announces publication of its phase 2, CervISA study in the peer-reviewed journal "Science Translational Medicine". The paper titled 'Strong vaccine responses during chemotherapy are associated with prolonged survival' can be found here: https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aaz8235.

The CervISA study was an open label, phase 2 study in patients with late stage HPV16 positive cervical cancer. Seventy-seven patients were treated with ISA Pharma's lead product, ISA101b, an HPV16-specific immunotherapeutic agent, in combination with standard-of-care (SoC) chemotherapy (carboplatin/paclitaxel). The addition of ISA101b to SoC chemotherapy led to a strong and highly specific anti-tumor immune response and significant improvement of patient survival in responding patients as evident from the following observations:

• A strong correlation was seen between strength of the HPV-specific immune response and overall survival (OS). There was significantly longer (p=0.012) overal survival in patients with a good immune response (median OS 16.8 months) compared to patients with a weak response (median OS 11.2 months).
• Additionally, 11 of the 14 patients still alive at the end of the study displayed a strong vaccine induced response and included 9 FIGO stage IVa-IVb patients who had a mean OS of 3 years, an encouraging indication of highly durable survival outcomes in responding patients.

Professor Kees Melief, Chief Scientific Officer of ISA Pharmaceuticals, said: "We previously demonstrated that standard-of-care carboplatin/paclitaxel chemotherapy reduces abnormally high numbers of immunosuppressive myeloid cells, while leaving T-cell levels unharmed¹. Timed SLP therapy creates a highly specific T-cell mediated immune response, during the chemotherapy regimen. With this study, conducted in close collaboration with Prof. Sjoerd van der Burg and colleagues of the Leiden University Medical Center and the Oncode Institute, we have now convincingly confirmed the complementary benefit of these two treatment modalities without any additional toxicity burden. This type of chemo-immunotherapy approach may be generally applicable across many cancer types if the vaccine ingredients are changed to tumor-associated or neoantigen-containing SLP instead of HPV-SLP."

Gerben Moolhuizen, Chief Executive Officer of ISA Pharmaceuticals, said: "This study provides valuable insights into how best to apply our immunotherapies in a late stage cancer clinical setting as well as in combination with standard-of-care chemotherapy. ISA Pharma is aiming to accelerate a number of novel SLP therapies into clinical development. We are happy to see such clear synergy between our SLPs and chemotherapy. A previous clinical study has also demonstrated a benefit of combining ISA101b with anti-PD1 therapy: a doubling of response rates and survival in Head and Neck cancer compared to the responses reported for anti-PD1 therapy alone². Our SLPs are thus expected to offer multiple options for advancing treatment of both pre-malignant and late stage cancers." 

About ISA Pharmaceuticals

ISA Pharma is an immunotherapy company developing treatments for various cancers and infectious diseases. ISA Pharma has best-in-class technology to stimulate and activate the human immune system, specifically T cells, to fight diseased or infected cells. ISA Pharma has an exclusive collaboration with Regeneron around its lead asset, ISA101b, an immunotherapy targeting human papillomavirus type 16 (HPV16)-induced cancer. ISA101b is currently in a randomized Phase 2 clinical trial for first line and second line HPV16-positive head and neck cancer, in combination with Libtayo® (cemiplimab-rwlc), a PD-1 antibody that is being jointly developed by Regeneron and Sanofi. For more information, please visit www.isa-pharma.com.

About ISA 101b

ISA101b is ISA Pharma's lead product and has a clear product approval pathway in several cancer indications. Regeneron has an option to license ISA101b based on the outcome of the ongoing Phase 2 study of ISA101b in combination with Libtayo for head and neck cancer.

ISA101b is a Synthetic Long Peptide (SLP^®)  therapeutic designed to mount a highly specific T-cell mediated attack by the immune system on tumors positive for human papilloma virus type 16 (HPV16). The product has successfully and safely completed multiple human clinical studies in over 200 patients

• ISA101 has been shown to be effective in patients with early stage, HPV 16 positive, premalignant cancers³
• In late stage, HPV16 positive cervical cancer ISA101b has been shown to act complementary to chemotherapy in terms of clinical benefits^1,4, Late stage cancer patients suffer from local and systemic immunosuppression by immune suppressive myeloid cells. Standard of care chemotherapy regimens such as carboplatin and paclitaxel deplete these immune supressive cells, whilst also having a direct anti-tumour effect and further enable ISA101b to effectively attack the cancer via a T-cell mediated immune response.
• Importantly in a Phase 2, open label, Proof of Concept study, ISA101b in combination with nivolumab (anti-PD1 antibody) has shown tumour response rates and overall survival approx. double to those seen with anti-PD1 monotherapy in 2^nd line head and neck cancer positive for HPV16².

ISA is currently carrying out a randomized, controlled  phase 2 trial of ISA101b in combination with Libtayo in head and neck cancer, under the agreement with Regeneron. Further clinical trials are under preparation.

About HPV16 positive cancers:

• Human papilloma virus (HPV) type 16 is known to induce certain cancers such as cervical cancer and head and neck cancer
• Despite prophylactic vaccinations HPV 16 induced cancers continue to be a significant health threat with over 500,000 newly diagnosed HPV 16 positive cancer patients p.a. worldwide and over 26,000 in the USA alone.

References

1.  Welters MJ, et al. Sci Transl Med. 2016
2.  Massarelli E, et al. JAMA Oncology. 2018
3.  Kenter G,  et al. New England J Med. 2009
4.  Melief C, et al. Sci Transl Med. 2020