Cervical Cancer: Light at the end of the tunnel • Vol. 3 Issue 03 · Feb 04, 2020

At Agenus, we are advancing our anti-CTLA-4 and anti-PD-1 antibodies in the clinic for the treatment of relapsed/refractory cervical cancer. We are excited about the potential of bringing the next generation treatments for this aggressive cancer. Importantly, we expect our next generation CTLA-4 antibody to have the potential of providing further improvements to patients with metastatic cervical cancer as well as other cancers where the addition of CTLA-4 has proven benefit such as renal cell carcinoma, melanoma, and colorectal and liver cancers.

On a more personal side, last week we had the opportunity to host cancer survivors along with Chef Lam at our headquarters in Lexington, MA. Our program focused on how nutrition can help our immune system battle cancer. The Agenus team engaged with cancer survivors by teaching attendees about the drug development process and hearing personal stories from cancer survivors.

Cervical Cancer: Light at the end of the tunnel

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 and regulatory plans and timelines, and the anticipated benefit of balstilimab, zalifrelimab, and AGEN1181 over currently available treatments for cervical cancer. These statements are subject to risks and uncertainties, including those described in our SEC filings

At Agenus, our objective is to work hard until we find a cure for all patients with cancer. In this issue, we feature a story from Kate Weissman, a cervical cancer survivor and a strong advocate for the community. We thank you, Kate, for sharing your story!

Kate Weissman: A SurvivorOne may think that women with cervical cancer just have surgeries and move on with their lives. This cannot be further from the truth. In reality, cervical cancer survivors like myself continue the battle with every doctor’s appointment, every scan, every day, hoping that there is not a new tumor or a new symptom to manage. We are left with lifelong complications that alter every corner of our lives.

I was diagnosed in October 2015 with Stage 2B cervical cancer. When I received the call from my doctor I was home alone. It was very surreal -- I practically levitated out of my body and immediately thought, “I’m 30 years old and going to die.” My husband came home a few minutes later and I shared my earth-shattering news with him. We were faced with the notion of being taken from one another.

After meeting with my oncologists at Dana Farber/Brigham & Women’s Hospital, we discovered the cancer was also in a lymph node and therefore a hysterectomy would not be effective. My team recommended radiation and chemotherapy as the first line of treatment.

I began treatment hopeful that the cancer would not spread further through my lymphatic system. The treatments ravaged my body. I experienced nausea, extreme fatigue, significant digestive issues, and I was riddled with anxiety. My parents traveled up to Boston as often as they could to help with my caretaking and it was a living nightmare that we all had to navigate through together.

I completed my treatment in late December of that year and waited three agonizing months until my next scan. The results showed that while the cancer was no longer on my cervix, it had spread through my lymphatic system to my para-aortic lymph nodes. We were devastated.

My oncologists immediately performed a lymphadenectomy and transferred me to Massachusetts General Hospital (MGH). At MGH, I was to undergo a different type of radiation called proton beam radiation therapy (along with chemotherapy). My team recommended the proton beam radiation because of the location of the lymph nodes and because it would spare my kidneys and bowels from harmful exposure. They said that with traditional radiation, surrounding healthy tissues and organs could be damaged.

Chef German Lam, Chef and Cancer Survivor and inspiring advocate to help patients with cancer.  

Approximately 570,000 new cases of cervical cancer and 311,000 deaths from this disease occurred in 20181. The peak age of developing cervical cancer  is 47 years. Approximately half of women with invasive cervical cancer are younger than 35 years of age at diagnosis2. Older women (> 65 years) account for another 10% of patients. Preventive measures and advances in immuno-oncology offer the promise of eradicating this deadly disease. Exploratory clinical trials have shown that combination therapies of CTLA-4 and PD-1 show the greatest potential in generating durable benefit in this and other aggressive cancers. In recent initial trials of advanced cervical cancer, the combination of anti-CTLA-4 and anti-PD-1 antibodies has shown ~20% response rates3. This compares to ~12% response with anti PD-1 monotherapy in similar patients4 and lower response with chemotherapy5.

Chairman and CEO Garo Armen and President and COO Jennifer Buell introducing Agenus.

Cervical Cancer: Light at the end of the tunnel • Vol. 3 Issue 03 · Feb 04, 2020Vol. 3 Issue 03 · Feb 04, 2020

there are a shocking number of cancer patients who are denied oncologist-recommended treatments because their insurance will not pay for expensive treatments. Insurance companies should not decide who lives and dies.

I have also become a fierce advocate for the cancer community, spreading awareness of cervical cancer, HPV (the virus that causes cervical cancer), and the HPV vaccination. Through my involvement with

the American Cancer Society Cancer Action Network, I have lobbied to both state and federal lawmakers in Massachusetts and on Capitol Hill imploring them to pass policies that will help patients and their families. I am proud that this past week, Governor Baker signed a proclamation I proposed declaring January Cervical Cancer Awareness Month in Massachusetts.

Through this journey and organizations like Cervivor (an organization dedicated to informing and empowering women and their families about cervical cancer), I have met countless other women who have experienced what I have. We suffer together, managing post-treatment symptoms and the daily anxiety the disease will come back. And we have mourned the loss of our fellow Cervivor sisters that have lost their battles along the way.

We can end this disease. We are rooting for Agenus and others to brings cures for cancer patients without the devastating lifelong side effects that cancer patients experience. Cervical cancer is caused by a virus we have a vaccination for. Women do not need to die or

suffer from this if we eliminate the stigma of HPV, spread awareness of the safety and efficacy of the vaccination, and provide all women, no matter where they live or what their socioeconomic standing is, access to screenings. We can be the generation that sees the last of this.

Over four years later since my diagnosis, I am cancer-free although I am still managing the physical, emotional, and financial consequences of cancer. Every day I work to keep my anxiety under control as I am still faced with the terrifying notion that it could come back.

My husband and I are undergoing the surrogacy process to bring children into this world, as I will never be able to carry. I take a birth control pill to manage my menopause symptoms caused by the radiation shutting my

Proton beam radiation therapy would be more targeted.

As we began preparations, we learned my insurance company was refusing to cover the treatment claiming the treatment was “experimental, investigational, and unproven” to a cervical cancer patient like myself – a clear contradiction to the evidence my oncologists presented. As a cancer patient, you are fighting for your life. Now you must fight for treatment that could potentially save you.

My husband and I worked closely with my doctors to appeal the insurance company’s denials. My oncologists grew anxious they wouldn’t be able to administer the radiation I needed. We engaged local lawmakers, representatives from the U.S. Department of Health and Human Services, experts in the field, and nothing changed the insurance company’s stance. All of this on top of the hardship of this disease was unreal. None of it mattered, and after six rounds of appeals we received our final denial letter. Pretty surreal to have your health insurance you pay a premium for unwilling to help in a time of a health crisis.

In an act of heroism, my parents reached into their retirement savings and paid the $100,000 cost of the treatment. I am incredibly lucky this was an option for me; most patients would not have this option.

I began this new radiation vand chemotherapy immediately. Fortunately, the treatments worked and a PET/CT scan in June showed no more evidence of cancer. My doctors recommended another round of chemotherapy that would eradicate anything microscopic lurking in my lymphatic system. This round of chemotherapy caused hair loss, something I had avoided up until this point. Losing my hair was very difficult, but the promise of surviving cancer was motivation enough to get me through.

References:

1. https://www.who.int/health-topics/cervical-cancer#tab=tab_1

2. https://www.cancernetwork.com/cancer-management/cervical-cancer

3. Naumann, RW. Efficacy and safety of nivolumab (Nivo) + ipilimumab (Ipi) in patients (pts) with recurrent/metastatic (R/M) cervical cancer: Results from CheckMate 358. Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

4. Chung, HC, et al. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results from the Phase II KEYNOTE-158 Study. J. Clinical Oncology. Available at: https://ascopubs.org/doi/full/10.1200/JCO.18.01265

5. Bookman, MA, et al. Topotecan in squamous cell carcinoma of the cervix: A Phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2000 Jun;77(3):446-9.

Cervical Cancer: Light at the end of the tunnel •

Kate Weissman: A Survivor, lobbied to both state and federal lawmakers in Massachusetts and on Capitol Hill imploring them to pass policies that will help patients and their families.

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 and regulatory plans and timelines, and the anticipated benefit of balstilimab, zalifrelimab, and AGEN1181 over currently available treatments for cervical cancer. These statements are subject to risks and uncertainties, including those described in our SEC filings.

ovaries down. The battle against cancer doesn’t stop when the chemo drip does.

In March, I filed a class action lawsuit against my insurance company for failing to uphold their fiduciary duty to me and others. I have learned