• Analyses of non-clinical study data demonstrate longer tumor retention with ¹⁷⁷Lu-FAP-2286 than ¹⁷⁷Lu-FAPI-46, resulting in greater tumor inhibition
• Phase 1 data is expected later this year from the ongoing LuMIERE clinical trial evaluating FAP-2286 as a therapeutic and imaging agent in multiple solid tumors
• Non-clinical evaluation of Rubraca in tumors with mutations in non-BRCA HRR genes showed similar efficacy to that observed in BRCA1/2-altered models

Clovis Oncology, Inc. (NASDAQ: CLVS), announced today that two abstracts featuring non-clinical data from studies evaluating FAP-2286 and Rubraca and a Trial-in-Progress poster detailing the Phase 1 portion of the LuMIERE study will be presented at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2022, being held April 8-13, 2022, in New Orleans.

In a new non-clinical data analysis, FAP-2286 demonstrated potent affinity for human fibroblast activation protein (FAP) by biochemical and cell-based assays. Additionally, lutetium-177 (¹⁷⁷Lu)-FAP-2286 showed longer tumor retention, resulting in greater tumor inhibition as compared to lutetium-177 (¹⁷⁷Lu)-FAPI-46, a FAP-targeted radiotracer developed for therapeutic applications at the University of Heidelberg, Germany.

FAP-2286 is the first peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting FAP to enter clinical development and the lead candidate in Clovis Oncology’s targeted radionuclide therapy (TRT) development program.

Approximately 50 patients will be enrolled in the Phase 1 portion of the multicenter, open-label LuMIERE trial, which is currently enrolling patients with advanced solid tumors (NCT04939610). The Phase 1 portion of the study is evaluating the safety of the investigational therapeutic agent ¹⁷⁷Lu-FAP-2286 and will identify the recommended Phase 2 dose and schedule. The safety and tumor uptake of the imaging agent gallium-68 (⁶⁸Ga)-FAP-2286 is also being evaluated. Once the Phase 2 therapeutic dose is determined, Phase 2 expansion cohorts in multiple tumor types are planned for later in 2022.

Separately, non-clinical data evaluating Rubraca efficacy in a panel of tumors with deleterious alterations in a core group of non-BRCA HRR genes showed responses similar to the efficacy observed in BRCA1/2-altered models. The goal of the studies was to investigate the in vitro and in vivo synthetic lethality activity of Rubraca in multiple cancer cell types and tumors harboring genetic or epigenetic alterations in non-BRCA HRR genes.

“The non-clinical data presented at AACR further show the potential of FAP-2286, our first targeted radiotherapy candidate, as a therapeutic and imaging agent and we look forward to sharing initial clinical data from the Phase 1 portion of the LuMIERE study of FAP-2286 later this year,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “We also remain committed to a greater understanding how patients with tumors associated with different genetic alterations may benefit from treatment with Rubraca.”

The following Clovis-sponsored posters and supplemental information will be available as of Friday, April 8 at 1:00 p.m. CDT at https://clovisoncology.com/pipeline/scientific-presentations/.

FAP-2286

Abstract #3317: Comparative biodistribution and radiotherapeutic efficacy of the fibroblast activation protein (FAP)-targeting agents FAP-2286 and FAPI-46

• Lead Author: Dirk Zboralski, Ph.D., 3B Pharmaceuticals GmbH, Berlin, Germany
• Poster Session: Preclinical Radiotherapeutics
• Date/Time: April 12, 1:30 – 5:00 p.m. CDT
• Key Takeaways: FAP-2286 demonstrated potent affinity for human FAP by biochemical and cell-based assays. ¹⁷⁷Lu-FAP-2286 showed longer tumor retention, resulting in greater tumor inhibition as compared to ¹⁷⁷Lu-FAPI-46. The prolonged tumor retention of FAP-2286 correlated with a higher intracellular accumulation.

Abstract #CT251: LuMIERE: A phase 1/2 study investigating safety, pharmacokinetics, dosimetry, and preliminary antitumor activity of ¹⁷⁷Lu-FAP-2286 in patients with advanced or metastatic solid tumors

• Lead Author: Jonathan McConathy, M.D., Ph.D., University of Alabama School of Medicine, Birmingham, AL.
• Poster Session: Phase I Trials in Progress 2
• Date/Time: April 13, 9:00 a.m. – 12:30 p.m. CDT
• Key Takeaways: Peptide-targeted radionuclide therapy directed toward FAP with the agent FAP-2286 has demonstrated antitumor activity in preclinical studies. LuMIERE (NCT04939610) is an ongoing phase 1/2, multicenter, open-label study evaluating safety and tolerability, pharmacokinetics (PK), dosimetry, and preliminary activity of the therapeutic agent ¹⁷⁷Lu-FAP-2286 in patients with a FAP-expressing solid tumor. Safety and tumor uptake of the imaging agent ⁶⁸Ga-FAP-2286 are also being evaluated.

For more information about FAP-2286, Targeted Radionuclide Therapy (TRT), or Clovis’ TRT development program, click here.

Rubraca

Abstract #1260: Nonclinical evaluation of rucaparib in tumors with mutations in non-BRCA1/2 homologous recombination repair (HRR) genes

• Lead Author: Liliane Robillard, M.S., Clovis Oncology, Inc., Boulder, CO.
• Poster Session: Biomarkers Predictive of Therapeutic Benefit 2
• Date/Time: April 11, 9:00 a.m. – 12:30 p.m. CDT
• Key Takeaways: In vitro small interfering ribonucleic acid (siRNA) knockdown of a subset of HRR genes showed synthetic lethality with rucaparib treatment in ovarian and prostate cancer cell lines. Rucaparib efficacy observed in patient-derived tumor xenograft (PDX) models with deleterious alterations in a core group of non-BRCA HRR genes was similar to the efficacy observed in BRCA1/2-altered models across different solid tumors, with enhanced sensitivity in tumors with biallelic alterations.

About FAP-2286

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use. High FAP expression has been shown in pancreatic ductal adenocarcinoma, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non–small cell lung, squamous head and neck cancers, and cancer of unknown primary. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade. Clovis holds US and global rights for FAP-2286 excluding Europe, Russia, Turkey, and Israel.

FAP-2286 is an unlicensed medical product.

About Targeted Radionuclide Therapy

Targeted radionuclide therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing delivery of radiation to normal tissue. Targeted radionuclides are created by linking radioactive isotopes, also known as radionuclides, to targeting molecules (e.g., peptides, antibodies, small molecules) that can bind specifically to tumor cells or other cells in the tumor environment. Based on the radioactive isotope selected, the resulting agent can be used to image and/or treat certain types of cancer. Agents that can be adapted for both therapeutic and imaging use are known as “theranostics.” Clovis, together with licensing partner 3B Pharmaceuticals, is developing a pipeline of novel, targeted radiotherapies for cancer treatment and imaging, including its lead candidate, FAP-2286, an investigational peptide-targeted radionuclide therapeutic (PTRT) and imaging agent, as well as three additional discovery-stage compounds.

About the LuMIERE Clinical Study

LuMIERE is a Phase 1/2 study evaluating FAP-2286 as a peptide-targeted radionuclide therapy (PTRT) targeting fibroblast activation protein, or FAP, in patients with advanced solid tumors. The Phase 1 portion of the LuMIERE study is evaluating the safety of the investigational therapeutic agent and will identify the recommended Phase 2 dose and schedule of lutetium-177 labeled FAP-2286 (¹⁷⁷Lu-FAP-2286). FAP-2286 labeled with gallium-68 (⁶⁸Ga-FAP-2286) will be utilized as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment with the therapeutic agent. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types.

About Rubraca (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca is an unlicensed medical product outside of the US and Europe

Rubraca US FDA Approved Indications

Ovarian Cancer

Rubraca is indicated for the maintenance treatment of adult women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Rubraca is indicated for the treatment of adult women with a deleterious BRCA mutation (germline and/or somatic)-associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca.

Prostate Cancer

Rubraca is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28 day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA damaging agents.

Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.

Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca. For males on Rubraca treatment who have female partners of reproductive potential or who are pregnant, effective contraception should be used during treatment and for 3 months following the last dose of Rubraca.

Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1-4) were nausea (76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%), constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia (29%), nasopharyngitis/upper respiratory tract infection (29%), stomatitis (28%), decreased appetite (23%), and neutropenia (20%).

Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1-4) were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea (21%), and thrombocytopenia (21%).

Co-administration of rucaparib can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring.

Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the last dose.

Please Click here for full Prescribing Information for Rubraca.

You may also report side effects to Clovis Oncology, Inc. at 1-415-409-7220 (US toll) or 1-844-CLVS-ONC (1-844-258-7662; US toll-free).

About Clovis Oncology

Clovis Oncology, Inc. is a biopharmaceutical company focused on acquiring, developing, and commercializing innovative anti-cancer agents in the US, Europe, and additional international markets. Clovis Oncology targets development programs at specific subsets of cancer populations, and simultaneously develops, with partners, for those indications that require them, diagnostic tools intended to direct a compound in development to the population that is most likely to benefit from its use. Clovis Oncology is headquartered in Boulder, Colorado, with additional office locations in the US and Europe. Please visit www.clovisoncology.com for more information.

To the extent that statements contained in this press release are not descriptions of historical facts regarding Clovis Oncology, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Examples of forward-looking statements contained in this press release include, among others, statements of our intentions and expectations for our development and discovery programs, including the timing and pace of pre-clinical development, plans for and expected timing and pace of clinical development, plans for additional applications of Rubraca and the FAP-2286 peptide, including potential indications, tumor types and combination trials, plans for presentation of data and regulatory plans with respect to Rubraca FAP-2286. Such forward-looking statements involve substantial risks and uncertainties that could cause Clovis Oncology’s actual results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in drug discovery and pre-clinical and clinical development, including the outcome of pre-clinical studies and clinical trials, whether initial results, findings or research will support future studies or development, whether future study results will be consistent with previous study findings or other results, including pre-clinical studies, results in named-patient or similar programs or clinical trials, whether additional studies not originally contemplated are determined to be necessary, the timing of initiation, enrollment and completion of planned studies and actions by the FDA, the EMA or other regulatory authorities regarding data required to support drug applications and whether to approve drug applications. Clovis Oncology undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the company in general, see Clovis Oncology’s Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and its other reports filed with the Securities and Exchange Commission.

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