Entry Into a Material Definitive Agreement

On January 20, 2022, Apellis Pharmaceuticals, Inc., a Delaware corporation (the "Company"), entered into an Open Market Sale AgreementSM (the "Agreement") with Jefferies LLC, as agent ("Jefferies"), pursuant to which the Company may offer and sell shares of its common stock, $0.0001 par value per share (the "Shares"), from time to time through Jefferies (the "Offering") (Filing, 8-K, Apellis Pharmaceuticals, JAN 20, 2022, View Source [SID1234605614]). The Company has also filed a prospectus supplement with the Securities and Exchange Commission (the "SEC") in connection with the Offering (the "Prospectus Supplement") under the Company’s existing automatic shelf Registration Statement on Form S-3 (File No. 333-235830), which became effective on January 7, 2020 (the "Registration Statement"). Pursuant to the Prospectus Supplement, the Company may offer and sell Shares having an aggregate offering price of up to $300.0 million.

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Upon delivery of a placement notice and subject to the terms and conditions of the Agreement, Jefferies may sell the Shares at market prices by any method deemed to be an "at the market offering" as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended (the "Securities Act"), including sales made directly on or through The Nasdaq Global Select Market ("Nasdaq"), the existing trading market for the Company’s common stock.

The Company or Jefferies may suspend or terminate the offering of Shares upon notice to the other party, subject to certain conditions. Jefferies will act as sales agent on a commercially reasonable efforts basis consistent with its normal trading and sales practices and applicable state and federal law, rules and regulations and the rules of Nasdaq.

The Company has agreed to pay Jefferies commissions for its services of acting as agent of up to 3.0% of the gross proceeds from the sale of the Shares pursuant to the Agreement. The Company has also agreed to provide Jefferies with customary indemnification and contribution rights.

A copy of the Agreement is attached as Exhibit 1.1 hereto and is incorporated herein by reference. The foregoing description of the material terms of the Agreement is qualified in its entirety by reference to such exhibit.

Wilmer Cutler Pickering Hale and Dorr LLP, counsel to the Company, has issued a legal opinion relating to the Shares. A copy of such legal opinion, including the consent included therein, is attached as Exhibit 5.1 hereto.

The Shares will be sold pursuant to the Registration Statement, and offerings of the Shares will be made only by means of the Prospectus Supplement. This Current Report on Form 8-K shall not constitute an offer to sell or solicitation of an offer to buy the Shares, nor shall there be any sale of the Shares in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities law of such state or jurisdiction.

Item 1.02
Termination of a Material Definitive Agreement.

In connection with the entry into the Agreement on January 19, 2022, the Company terminated its prior amended and restated equity distribution agreement, dated as of October 4, 2019, by and among the Company, Citigroup Global Markets Inc. ("Citigroup") and Jefferies (the "Prior Agreement"), in accordance with its terms. The Prior Agreement provided for Citigroup and Jefferies to sell shares of common stock having an aggregate offering price of up to $150.0 million by any method deemed to be an "at the market offering" as defined in Rule 415(a)(4) promulgated under the Securities Act. The Company cannot make any further sales of its common stock pursuant to the Prior Agreement.

Senhwa’s Silmitasertib Receives US FDA Orphan Drug Designation for the Treatment of Biliary Tract Cancer

On January 20, 2022 Senhwa Biosciences, Inc. (TPEx: 6492), a drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and novel coronaviruses, announced that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for Silmitasertib, a highly selective inhibitor of casein kinase 2 (CK2) to treat patients with Biliary Tract Cancer (Press release, Senhwa Biosciences, JAN 20, 2022, View Source [SID1234605633]).

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"We are pleased to receive ODD for Silmitasertib for the treatment of Biliary Tract Cancer, a rare, malignant disease for which there are no effective therapies. ODD represents an important regulatory milestone that has the potential to expedite the clinical development of Silmitasertib, which is a potent and selective CK2 inhibitor," said Mei-Hui Kuo, Acting Chief Executive Officer of Senhwa Biosciences.

The US FDA grants ODD status to drugs and biologics that are intended to treat, prevent or diagnose a life-threatening or chronically debilitating rare disease with a prevalence of fewer than 200,000 people in the US. ODD affords certain financial incentives to support clinical development, including the potential for up to seven years of market exclusivity, in the US upon regulatory approval.

Biliary tract cancer (BTC) refers to a group of rare, diverse and aggressive cancers that arise from the bile duct system. BTCs are classified into four distinct subtypes based on the tissue where the cancer originates including intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC), gallbladder cancer (GBC) and ampullary cancer.

In its early-stages, patients with BTC often present with nonspecific symptoms which can complicate and delay diagnosis. Patients with BTC are usually diagnosed when the disease has already advanced and/or spread. First-line standard of care is a chemotherapy regimen of gemcitabine + cisplatin. There are no globally accepted standards of care for locally advanced or metastatic BTC after first line chemotherapy has failed. Pre-clinical studies demonstrate that inhibition of CK2 by Silmitasertib prevents DNA repair, induces apoptosis, and improves the antitumor activity of gemcitabine and cisplatin. There is a significant need for new BTC treatment options.

About Silmitasertib

Silmitasertib is a first-in-class small molecule drug that targets the CK2 pathway and acts as a CK2-inhibitor. Clinical studies thus far have shown Silmitasertib to be safe and well-tolerated in humans and is easily administered due to its oral formulation. Silmitasertib is currently under development in several oncology programs in adults and children with recurrent/advanced or metastatic cancer. To date, three Phase I trials and one Phase II trial of Silmitasertib in cancer patients have been completed; currently, there are two ongoing Phase II studies of Silmitasertib.

The US FDA has granted Silmitasertib key drug designations: Orphan Drug Designation for the treatment of Cholangiocarcinoma in December 2016, Rare Pediatric Disease Designation and Orphan Drug Designation for the treatment of Medulloblastoma in July 2020 and December 2021, respectively. Fast Track Designation was granted in August 2021 for the treatment of recurrent Sonic Hedgehog driven Medulloblastoma.

Volition presents study data at ASCO GI 2022 on circulating nucleosomes for the detection of colorectal cancer and high-risk advanced adenomas

On January 20, 2022 VolitionRx Limited (NYSE AMERICAN: VNRX) ("Volition"), a multi-national epigenetics company, reported the results of two large scale clinical studies, which show that the company’s Nu.Q assays, when used in conjunction with the Fecal Immunochemical Test (FIT), can detect colorectal cancer and all high-risk advanced adenomas in symptomatic patients, and thereby reduce unnecessary colonoscopies (Press release, VolitionRX, JAN 20, 2022, View Source [SID1234605651]). The studies also demonstrated that the company’s Nu.Q assays can improve the detection of high-risk adenomas in asymptomatic patients.

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Principal Investigator, Professor Han-Mo Chiu, National Taiwan University, said "We are enormously encouraged by the findings of these two studies. Not only do they show that using Nu.Q assays in combination with FIT can potentially reduce unnecessary colonoscopies by up to 28% in patients with gastrointestinal symptoms, the studies also show that this dual approach could be used more widely to improve the effectiveness of FIT-based screening programs targeting asymptomatic patients. We look forward to presenting our findings to colleagues at ASCO (Free ASCO Whitepaper) GI 2022."

Dr. Marielle Herzog, Research and Development Director at Volition, said "Early diagnosis is key to improving outcomes for patients with colorectal cancer, and cancer screening programs are critical to every public health system. The results of our studies, using Volition’s Nu.Q assays in conjunction with FIT, are incredibly encouraging, not only in reducing unnecessary colonoscopies but also in detecting high-risk adenomas, both proximal and distal, which FIT, when used alone can miss. We are excited about the next stage, facilitating an independent, prospective validation study later this year."

The studies were undertaken by Volition and the Department of Internal Medicine at the National Taiwan University Hospital and findings will be presented at the 2022 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, later this week.

Volition is developing simple, easy to use, cost-effective blood tests to help diagnose and monitor a range of life-altering diseases including cancer.

Colorectal cancer is the fourth most common cancer worldwide, with 1.9 million new cases in 2020, and accounts for over 9% of all cancer-related deaths each year¹. Population-based colorectal cancer screening programs are in place in many healthcare systems globally, and the most commonly recommended screening method² is the FIT, followed up with colonoscopy, an invasive visual examination. However, approximately 60% of FITs provide false-positive results³, leading to unnecessary and costly colonoscopies.

Posters to be presented at ASCO (Free ASCO Whitepaper) GI 2022 can be downloaded here:

1) Circulating nucleosomes levels improve FIT performance for detecting high-risk colorectal neoplasms in a symptomatic population.
2) Circulating nucleosomes for detection of colorectal cancer and high-risk advanced adenomas.

For more information about Volition’s Nu.Q technology go to: www.volition.com

Notes to editors:

References:

¹ World Health Organization International Agency for Research on Cancer (IARC). GLOBOCAN 2020: estimated cancer incidence, mortality and prevalence worldwide in 2020.

² Schliemann, D., Ramanathan, K., Matovu, N. et al. The implementation of colorectal cancer screening interventions in low-and middle-income countries: a scoping review. BMC Cancer 21, 1125 (2021).

³ Chiu HM, Chen SL, Yen AM, et al. Effectiveness of fecal immunochemical testing in reducing colorectal cancer mortality from the One Million Taiwanese Screening Program. Cancer. 2015;121(18):3221-3229.

About the studies

476 patients referred for surveillance colonoscopy or secondary to bowel symptom were enrolled: (i) CRC (n= 67), (ii) advanced adenoma (AA) (n=60), non-AA (n=123); (iv) non-neoplastic polyps (n=29); (vi) colonoscopy negative (controls) (n=197).
520 average-risk asymptomatic patients: (i) CRC (n= 33), (ii) advanced adenoma (AA) (n=123, including 18 with AA>2cm); (iii) non-AA (n=168); (iv) non-neoplastic polyps (n=30); (vi) colonoscopy negative control (n=166).
Plasma and stool samples were obtained prior to colonoscopy.
Circulating Nucleosome levels measured using Volition’s Nu.Q quantitative immuno-assays.
FIT: OC-SENSOR (Eiken Chemical Co., Ltd., Tokyo, Japan) using a positive cut-off of 20ug/g feces.

AVEO Oncology Presents Three Posters for Tivozanib/Immunotherapy Combinations at the 2022 ASCO GI Cancers Symposium

On January 20, 2022 AVEO Oncology (Nasdaq: AVEO), a commercial stage, oncology-focused biopharmaceutical company, reported that new efficacy and safety data from the first line (cohort A) of the phase 1b/2 DEDUCTIVE study of FOTIVDA (tivozanib) in combination with IMFINZI (durvalumab) in previously untreated metastatic hepatocellular carcinoma (HCC) are being presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (ASCO GI) Cancers Symposium (Press release, AVEO, JAN 20, 2022, View Source [SID1234605615]). In addition, two trials in progress posters are being presented, which showcases cohort B of the DEDUCTIVE HCC study that is currently enrolling HCC patients following prior bevacizumab and atezolizumab; and the Company, in collaboration with the University of Florida Health Cancer Center, is presenting the study design for the Phase 1b/2 IMMCO-1 trial of atezolizumab plus tivozanib in immunologically cold pancreatic, gallbladder and biliary cancers.

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"We believe that the safety and efficacy data observed in cohort A of the Phase 2 portion of the DEDUCTIVE study continue to support the development of tivozanib to serve as an attractive VEGFR TKI to use in combination with durvalumab in first line HCC patients," said Michael Bailey, President and Chief Executive Officer of AVEO. "The poster presentations at this year’s ASCO (Free ASCO Whitepaper) GI conference reflect the expanding scope of our pipeline as we leverage the potential efficacy of our lead program tivozanib through a combination strategy targeting a number of cancers."

Topline Efficacy and Safety Data Poster Title: A Phase 1b/2 Study of Tivozanib in Combination with Durvalumab in Subjects with Advanced Hepatocellular Carcinoma (DEDUCTIVE): Efficacy Results in Previously Untreated Patients (Abstract #462 / Poster: M10)

The Company will present topline data for cohort A of the DEDUCTIVE study, which is assessing the safety and efficacy of tivozanib in combination with IMFINZI (durvalumab), AstraZeneca’s human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with unresectable locally advanced or metastatic, previously untreated HCC. A total of 20 patients with advanced or metastatic HCC were enrolled in cohort A of the Phase 2 portion of the study safety and efficacy of tivozanib plus durvalumab. Patients received 0.89 mg of tivozanib orally once daily for 21 days followed by seven days off therapy in combination with 1500 mg of durvalumab intravenously (IV) on day one given every four weeks, on a 28 day cycle. The combination was well tolerated, with three patients showing Grade 3 TRAEs, and no Grade 4 TRAEs or treatment-related deaths. The combination demonstrated a 27.8% partial response (PR) rate and disease control rate (PR + stable disease) 67.8%, with a median PFS of 7.3 months and a 1-year OS of 76%, which positions the tivozanib combination well relative to other VEGF ICI combinations in the setting.

Trials in Progress Poster Presentation titled: A Phase 1b/2 Open Label Study of Tivozanib in Combination with Durvalumab in Subjects with Advanced Hepatocellular Carcinoma: DEDUCTIVE – (Abstract: TPS499 / Poster: Online Only)

The DEDUCTIVE study is a multicenter, open-label study to evaluate the safety, tolerability, and efficacy of tivozanib in combination with durvalumab in subjects with advanced HCC previously untreated (cohort A) or bevacizumab- and atezolizumab-pretreated HCC (cohort B). Cohort A is fully enrolled and cohort B will enroll up to 20 subjects. Cohort A showed a promising safety and efficacy profile in previously untreated patients and cohort B has the potential demonstrate the first clinical study results in the emerging population of prior bevacizumab and atezolizumab treated patients.

The rationale for a combination therapy of tivozanib plus durvalumab to treat HCC draws on the potential synergistic mechanisms of tivozanib and durvalumab to remove inhibition of the immune response that mediates antitumor activity. The selectivity and favorable tolerability of the VEGFR TKI tivozanib may allow it to be used as a combination therapy with an immune checkpoint inhibitor, such as durvalumab.

The DEDUCTIVE trial is being conducted as part of a clinical collaboration between AVEO and AstraZeneca. AVEO is serving as the study sponsor.

Trials in Progress Poster Presentation titled: A phase 1b/2 study (IMMCO-1) of atezolizumab plus tivozanib in immunologically cold pancreatic, gallbladder, and biliary cancers – (Abstract: TPS491 / Poster: N8)

The ongoing IMMCO-1 study is an open-label, non-randomized Phase 1b/2 signal seeking basket study of the combination of the tivozanib and atezolizumab in multiple immunologically cold tumors, including pancreatic, gallbladder and biliary cancers. The co-primary endpoints are safety and efficacy. The Phase 1b portion will assess the safety profile of the combination of tivozanib and atezolizumab with a potential dose de-escalation of tivozanib using a 3+3 study design to yield a recommended Phase 2 dose.

VEGF is thought to play a key role in modulating the anti-tumor immune response. In addition, VEGF inhibits dendritic cell differentiation, limiting the presentation of tumor antigens to CD4 and CD8 T cells. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade. Combined use of a VEGF tyrosine kinase inhibitor (TKI) and checkpoint inhibitor is already standard of care in advanced kidney, cervical and endometrial cancers. There has been suggestion that such a combination may have clinical activity in some microsatellite stable (MSS) GI malignancies.

The Phase 2 portion is expected to enroll up to 26 additional patients using the recommended Phase 2 dose using the Simon two-stage design of recruitment. This signal seeking study is looking to confirm the best objective response rate for evaluable patients increasing from < 7% (null hypothesis) to 25% (one-sided alpha = 0.05; 80% power).

The three posters to be presented at the 2022 ASCO (Free ASCO Whitepaper) GI Cancers Symposium are available on the Publications page of the AVEO Oncology website (click here). Details on the presentation are available on the 2022 ASCO (Free ASCO Whitepaper) GI website (click here).

About FOTIVDA (tivozanib)

FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models.2 FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.
Females and Males of Reproductive Potential: Can impair fertility.
Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FOTIVDA Full Prescribing Information which is available at www.FOTIVDA.com.

About Advanced Renal Cell Carcinoma

According to the American Cancer Society’s 2021 statistics, renal cell carcinoma (RCC) is the most common type of kidney cancer, which is among the ten most common cancers in both men and women. Approximately 73,750 new cases of kidney cancer will be diagnosed annually and about 14,830 people will die from this disease. In patients with late-stage disease, the five-year survival rate is 13%. Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC.3 According to a 2019 publication, 50% of the approximately 10,000 patients who progress following two or more lines of therapy choose not to receive further treatment,4 which may be attributable to tolerability concerns and a lack of data to support evidence-based treatment decisions in this highly relapsed or refractory patient population.

Oncolytics Biotech® Provides Enrollment Update on Multi-Indication Phase 1/2 Gastrointestinal Cancer Trial at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium

On January 20, 2022 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported an enrollment update on the phase 1/2 GOBLET study in a poster presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI) (Press release, Oncolytics Biotech, JAN 20, 2022, View Source [SID1234605634]).

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The GOBLET study is being managed by AIO, a leading academic cooperative medical oncology group based in Germany, and is designed to evaluate the safety and efficacy of pelareorep in combination with Roche’s anti-PD-L1 checkpoint inhibitor atezolizumab in patients with metastatic pancreatic, metastatic colorectal, and advanced anal cancers. The study includes three-patient safety run-ins for two of its four cohorts (first-line metastatic pancreatic and third-line metastatic colorectal cancer). Enrollment in these safety run-ins is complete. The study remains ongoing and is expected to enroll patients at 14 clinical trial sites across Germany.

"There is a pressing unmet need for agents that can synergize with immune checkpoint inhibitors (ICI) in gastrointestinal (GI) cancers, as fewer than half of these patients respond to ICI monotherapy," said Dirk Arnold M.D., Ph.D., Director of Asklepios Tumorzentrum Hamburg, and primary investigator of the GOBLET trial. "These low response rates are driven by immunosuppressive tumor microenvironments, which pelareorep has been shown to reverse in prior clinical studies in GI, breast, and hematological cancers. We thus believe pelareorep can increase the proportion of GI cancer patients responding to checkpoint inhibitors and are seeking to validate this hypothesis in the GOBLET study. We are very pleased with the trial’s progress to date and look forward to its continued advancement."

The GOBLET study builds on previously reported clinical proof-of-concept data for pelareorep-checkpoint inhibitor combination therapy in pancreatic cancer (link to PR, link to poster). It is also supported by prior early clinical data showing that pelareorep-based combination treatments stimulated an adaptive immune response and led to a greater than 90% clinical benefit rate in KRAS-mutated colorectal cancer patients (link to PR, link to study) and a greater than 80% increase in progression-free survival in pancreatic cancer patients with low levels of CEACAM6 expression (link to PR, link to poster). In addition to evaluating the safety and efficacy of pelareorep-atezolizumab treatment, the study also seeks to demonstrate the potential of CEACAM6 and T cell clonality as predictive biomarkers, which may allow selection of the most appropriate patients in future registration studies and increase their likelihood of success.

A copy of the ASCO (Free ASCO Whitepaper)-GI poster titled, "GOBLET: A phase 1 / 2 multiple-indication biomarker, safety, and efficacy study in advanced or metastatic gastrointestinal cancers exploring treatment combinations with pelareorep and atezolizumab," will be available on the Posters & Publications page of Oncolytics’ website (LINK) following the conclusion of the symposium.

About GOBLET
The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication study in advanced or metastatic gastrointestinal tumors. The study is being conducted at 14 centers in Germany. The co-primary endpoints of the study are objective response rate (ORR) assessed at week 16 and safety. Key secondary and exploratory endpoints include additional efficacy assessments and evaluation of potential biomarkers (T cell clonality and CEACAM6). The study employs a Simon two-stage design with Stage 1 comprising four treatment groups expected to enroll a total of approximately 55 patients:
1.Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line metastatic pancreatic cancer patients (n=12);
2.Pelareorep in combination with atezolizumab in 1st line MSI (microsatellite instability)-high metastatic colorectal cancer patients (n=19);
3.Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients (n=14); and
4.Pelareorep in combination with atezolizumab in 2nd line advanced and unresectable anal cancer patients (n=10).

Any cohort showing an ORR above a pre-specified threshold in Stage 1 may be advanced to Stage 2 and enroll additional patients.

About AIO
AIO-Studien-gGmbH (AIO) emerged from the study center of the internal oncology working group within the German Cancer Society (DKG). AIO operates with a non-profit purpose of promoting science and research with a focus on internal oncology. Since its foundation, AIO has become a successful sponsor and study management company and has established itself both nationally and internationally.

About Gastrointestinal Cancer
Excluding skin cancers, colorectal cancer is the third most common cancer, with an estimated 104,270 new cases of colon cancer and 45,230 new cases of rectal cancer expected to be diagnosed in the U.S. in 20211. Also, for the 2021 year, the American Cancer Society estimates there will be 60,430 new cases of pancreatic cancer2 and 9,090 new cases of anal cancer3 in the U.S.