AgenusNews • Vol. 3 • Issue 22 • Nov 3, 2020

Agenus therapies bring hope to cancer patients

This is The Story of a Cervical Cancer Survivor

Lurdes de Fátima Cavalheiro da Rosa is a cervical cancer survivor who was treated with the combination of balstilimab (anti-PD-1) and zalifrelimab (anti-CTLA-4) in our clinical trial. Less than two months after receiving treatment, Lurdes’ tumor was regressing; she is currently in remission with her tumor having shrunk more than 90%.

Lurdes lives in a small town in Brazil’s countryside. At the age of 51, her diagnoses devastated her and her family. She began radiation, brachytherapy, and chemotherapy, but these treatments did not work and her cancer continued to progress. Her last chemotherapy course left her significantly debilitated. Her doctors told her she had about four months to live. At this point, she wanted to try innovative therapies since conventional therapies had not helped. At first, she did not have access to these therapies as there were no open clinical trials for cervical cancer patients in Brazil. Her physician, Dr. Fránke, had heard about Agenus’ balstilimab and zalifrelimab clinical trial in the U.S.

Agenus, in collaboration with Orphan DC, an expert transport team supporting clinical trials, brought Lurdes to the U.S. She received treatment at Boca Raton Clinical Research in Miami, under the care of Dr. Amin. After only 5 infusions, she felt a renewed sense of energy. Lurdes’ cancer has shrunk 90% – she considers herself cured. Currently, she is continuing with balstilimab/zalifrelimab infusions at Hospital de Caridade de Ijuí in Brazil, but she is symptom-free. She is now an enthusiastic advocate for clinical trials, as she believes participation in our trial saved her life.

Cervical cancer is the fourth most common cancer in women, killing >300,000 women worldwide in 2018 alone. Preventable measures such as HPV vaccination and early pap-smear screenings exist for prevention and early detection of disease. With an early diagnosis, the cancer can be easily treated with a survival rate of ~92%. Unfortunately, many women across the US and developing countries have limited access to screening. Without this, cervical cancer is not detected until it has advanced and become increasingly difficult to treat.

Late-stage cervical cancer (IV) is diagnosed when the cancer has spread beyond the cervix into neighboring organs or distant locations of the body; this was the case with Lurdes. Most women diagnosed with advanced cervical cancer are first treated with chemotherapy in combination with another drug, Avastin. However, even with the addition of Avastin, the disease uniformly progresses and becomes fatal for most patients. The final line of approved therapy is Keytruda (anti-PD-1 agent). Keytruda is approved for a subset of patients with tumors that express a biomarker protein, PD-L1. As many as 60% of cervical cancer patients are ineligible to receive Keytruda because their tumors are PD-L1 negative. Even with this biomarker, only 14% of patients respond to Keytruda.

In sum, current therapies are ineffective for most women with cervical cancer. It remains a nearly incurable disease. Agenus is working to improve these outcomes for cervical cancer patients with our two immunotherapies, balstilimab and zalifrelimab. Response rates demonstrated with balstilimab monotherapy and balstilimab in combination with zalifrelimab are 14% and 22% respectively. These responses are seen in all patients regardless of their tumor biomarker status; however, response rates are even higher in patients with a PD-L1 positive tumor (19% and 27% respectively). We are very encouraged by the fact that responses seen in our trials are long-lasting. The median duration of response with monotherapy is 15.4 months, and is not yet reached with the combination, with some responses exceeding 16.6 months. Patients also tolerate our treatment well. Our therapies leverage the body’s own immune system; hence patients avoid the harsh toxicities associated with chemotherapy and radiation.

Agenus is also dedicated to ensuring that all cervical cancer patients who need our therapies have access to them. Lurdes’ story is one such example. As seen in Lurdes’ case, immunotherapies are currently inaccessible to many patients, particularly those in the developing world. In the United States, patients in poor areas lack insurance and transportation and therefore, are disproportionately affected by the disease without access to timely treatment. In addition, some patients may have to pay a steep list price to access these therapies, up to $10,000 per month. This acts as a significant barrier to receive care and contributes to higher mortality. At Agenus, our deep immuno-oncology pipeline gives us the independence to advance proprietary combinations with affordable pricing. We have initiated our rolling BLA submission of balstilimab, which is currently under FDA review. Our next steps will be to promptly explore the filing of balstilimab and zalifrelimab combination. By bringing our therapies to the market, we hope to transform the lives of many more cervical cancer patients and patients with many other cancers.

Forward-Looking Statements: This Agenus Newsletter includes forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding clinical development and regulatory plans and timelines. These statements are subject to risks and uncertainties, including those described in our SEC filings.