On October 3, 2022 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported that its board of directors has set October 26, 2022 as the record date (Record Date) for the dividend of shares of common stock of OmniAb, Inc. to be distributed to Ligand shareholders in order to effect the separation of Ligand and OmniAb into two independent, publicly traded companies (Press release, Ligand, OCT 3, 2022, View Source [SID1234621619]). The dividend in OmniAb shares is expected to be distributed to Ligand shareholders on or about November 1, 2022, the expected closing date of the previously announced business combination (Business Combination) between OmniAb and Avista Public Acquisition Corp. II (APAC) (NASDAQ: AHPA). Following the closing of the Business Combination, APAC will change its name to "OmniAb, Inc." (New OmniAb) and begin trading on the Nasdaq Global Market under the stock ticker symbol "OABI," and Ligand will continue to trade on the Nasdaq Global Market under the stock ticker symbol "LGND."

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Ligand shareholders as of the close of business on the Record Date will receive shares of OmniAb common stock on a pro rata basis representing 100% of Ligand’s interest in OmniAb. Immediately following the distribution of OmniAb shares, the Business Combination is expected to close. Upon the closing of the Business Combination, all shares of OmniAb common stock will be automatically exchanged for shares of New OmniAb on a pro rata basis according to a base exchange ratio (Base Exchange Ratio) calculated immediately prior to closing using a formula set forth in the merger agreement (Merger Agreement) among Ligand, OmniAb, APAC and a subsidiary of APAC. The Base Exchange Ratio is based on the number of shares of Ligand common stock outstanding and the relative trading values of the Ligand common stock in the "regular way" and "ex-distribution" markets during the five-trading-day period prior to the closing.

Based on an illustrative record date of June 30, 2022 and Ligand stock price as of such date and an estimated Base Exchange Ratio, Ligand shareholders would receive approximately 4.9 shares of New OmniAb common stock for each share of Ligand/OmniAb common stock.

In addition, as part of the exchange, Ligand shareholders as of the Record Date will receive earnout shares (Earnout Shares) of New OmniAb common stock on a pro rata basis according to an earnout exchange ratio (Earnout Exchange Ratio) calculated immediately prior to closing using a formula set forth in the Merger Agreement. Based on an illustrative record date of June 30, 2022 and Ligand stock price as of such date and an estimated Earnout Exchange Ratio, Ligand shareholders would receive approximately 0.75 shares of New OmniAb common stock for each share of Ligand/OmniAb common stock. The Earnout Shares will vest based upon the achievement of certain volume-weighted average trading prices for shares of New OmniAb during the five-year period following the closing of the Business Combination.

Based on the foregoing estimates, Ligand’s shareholders would receive aggregate shares of New OmniAb common stock representing approximately 76.3% (assuming no redemptions by APAC shareholders) to 85.0% (assuming maximum redemptions by APAC shareholders) of New OmniAb, APAC’s existing public shareholders would own approximately 18.0% (assuming no redemptions by APAC shareholders) to 0% (assuming maximum redemptions by APAC shareholders) of New OmniAb, and the sponsor and related parties of APAC (Sponsor) would own approximately 5.7% (assuming no redemptions by APAC shareholders) to 15.0% (assuming maximum redemptions by APAC shareholders) of New OmniAb, including the Earnout Shares in each case.

The actual number of shares of New OmniAb common stock and Earnout Shares that each Ligand shareholder will receive with respect to each share of OmniAb common stock will be calculated on the closing date and may differ from these estimates. No fractional shares of New OmniAb common stock will be issued in the merger, and instead Ligand shareholders will receive cash in lieu of any fractional share (other than with respect to Earnout Shares).

Ligand shareholders do not need to take any action. Their OmniAb shares received upon distribution of the dividend will automatically be exchanged for New OmniAb common stock and Earnout Shares in the merger on the closing date of the Business Combination. Following the closing of the Business Combination, Ligand shareholders will continue to hold, along with their new shares of New OmniAb common stock and Earnout Shares, the same number of shares of Ligand common stock that they held immediately prior to the closing. After the closing, investors should expect that Ligand’s share price will adjust to reflect the transfer of the OmniAb business to New OmniAb.

In connection with the Business Combination, OmniAb and APAC filed registration statements with the Securities and Exchange Commission (SEC), described below under "Important Information and Where to Find It." On September 30, 2022, the SEC declared both registration statements effective. The registration statements contain further information regarding the spin-off and Business Combination, including the conditions to completion of the Business Combination and additional details regarding the calculation of the applicable exchange ratios described above.

Factors that May Affect the Dividend and Spin-Off

The dividend is conditioned upon, and the spin-off and Business Combination are subject to, the satisfaction or waiver of closing conditions for the Business Combination. If certain closing conditions are not satisfied or waived in advance of the expected closing date, Ligand may elect to change the record date for the dividend to a later date or to not proceed with the dividend or the spin-off.

Two-Way Trading to Begin for Ligand on the Nasdaq Global Market (Nasdaq)

Beginning on or around the trading day prior to the Record Date and continuing through the close of trading on the closing date of the Business Combination, there will be two markets in Ligand common stock on Nasdaq: a "regular way" market and an "ex-distribution" market. During this period of two-way trading in Ligand common stock, there will also be a market on Nasdaq for New OmniAb common stock on a "when issued" basis.

The trading options that will be available during the two-way trading period are:

Ligand Regular Way Trading

If, during the period of two-way trading, a Ligand shareholder sells a share of Ligand common stock in the regular way market under Ligand’s Nasdaq symbol, "LGND," the shareholder will be selling both the share of Ligand common stock and the right to receive shares of New OmniAb common stock in the transaction.

Ligand Ex-distribution Trading

If, during the period of two-way trading, a Ligand shareholder sells a share of Ligand common stock in the ex-distribution market under the temporary Nasdaq symbol "LGNDV," the Ligand shareholder will be selling only a share of Ligand common stock and will retain the right to receive shares of New OmniAb common stock in the transaction.

New OmniAb When issued Trading

During the two-way trading period, a Ligand shareholder also has the option of selling the right to receive shares of New OmniAb common stock while retaining shares of Ligand common stock. This option will be available under the temporary Nasdaq symbol "OABIV."

Trades under the symbols "OABIV" and "LGNDV" will settle after the closing date of the Business Combination. If the transaction is not completed, all trades made under these temporary symbols will be cancelled.

In all cases, investors should consult with their financial and tax advisors regarding the specific implications of selling shares of their Ligand common stock or the right to receive shares of New OmniAb common stock on or before the closing date of the Business Combination.

About OmniAb

OmniAb’s discovery platform provides pharmaceutical industry partners access to the diverse antibody repertoires and high-throughput screening technologies to enable discovery of next-generation therapeutics. At the heart of the OmniAb platform is the Biological Intelligence (BI) of our proprietary transgenic animals, including OmniRat, OmniChicken and OmniMouse that have been genetically modified to generate antibodies with human sequences to facilitate development of human therapeutic candidates. OmniFlic (transgenic rat) and OmniClic (transgenic chicken) address industry needs for bispecific antibody applications though a common light chain approach, and OmniTaur features unique structural attributes of cow antibodies for complex targets. We believe the OmniAb animals comprise the most diverse host systems available in the industry and they are optimally leveraged through computational antigen design and immunization methods, paired with high-throughput single B cell phenotypic screening and mining of next-generation sequencing datasets with custom algorithms to identify fully human antibodies with superior performance and developability characteristics. An established core competency focused on ion channels and transporters further differentiates our technology and creates opportunities in emerging target classes. OmniAb antibodies have been leveraged across modalities, including bispecific antibodies, antibody-drug conjugates and others. The OmniAb suite of technologies span from BI-powered repertoire generation to cutting edge antibody discovery and optimization offering a highly efficient and customizable end-to-end solution for the growing discovery needs of the global pharmaceutical industry.

On October 3, 2022 Boston Scientific Corporation (NYSE: BSX) reported that it will webcast its conference call discussing financial results and business highlights for the third quarter ended September 30, 2022 on Wednesday, October 26, 2022 at 8:00 a.m. EDT (Press release, Boston Scientific, OCT 3, 2022, View Source [SID1234621618]). The call will be hosted by Mike Mahoney, chairman and chief executive officer, and Dan Brennan, executive vice president and chief financial officer. The company will issue a news release announcing financial results for the third quarter on October 26 prior to the conference call.

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A live webcast and replay of the webcast will be accessible at investors.bostonscientific.com. The replay will be available approximately one hour following the completion of the event.

On October 3, 2022 Viewpoint Molecular Targeting, Inc. ("Viewpoint" or the "Company"), a radiopharmaceutical company developing precision lead-212-based α-particle oncology therapeutics and complementary diagnostic imaging agents, reported that the U.S. Food and Drug Administration (FDA) has granted fast track designation for the development of [212Pb]VMT-α-NET for treatment of patients with SSTR2-positive unresectable or metastatic neuroendocrine tumors (NETs) (including GEP-NETs or bronchial NETs and pheochromocytomas and paragangliomas) (Press release, Viewpoint Molecular Targeting, OCT 3, 2022, https://viewpointmt.com/viewpoint-molecular-targeting-announces-vmt-net-granted-u-s-fda-fast-track-destination-for-the-treatment-of-neuroendocrine-tumors/ [SID1234621617]).

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"Although several exciting new medicines have emerged in the past decade for patients with neuroendocrine tumors, there remains an unmet need for certain patient segments, where survival rates remain low" said Dr Frances Johnson, M.D., COO and co-founder of Viewpoint. Added Michael Schultz, Ph.D., CSO and co-founder of Viewpoint, "we applied for fast track designation based on the compelling results seen in head-to-head animal studies and are appreciative of the FDA being able to review the data expeditiously." The Company expects the results of those studies to be presented publicly at the upcoming European Association of Nuclear Medicine (EANM) conference to be held October 15-19, 2022 in Barcelona, Spain.

"We are thrilled to receive FDA Fast Track Designation for our leading program," said Thijs Spoor, CEO of Viewpoint. "This designation will allow us to actively explore the fastest ways to bring our personalized alpha-particle theranostics to patients."

The FDA Fast Track Designation is one of several approaches utilized by the FDA to expedite development and review of potential medicines for serious conditions and that fulfill unmet medical needs. A potential new medicine may fill an unmet medical need by being the first therapy to address a specific serious condition, offer clinically significant advantages over available therapies, act via a different mechanism of action than available therapies, or have a benefit in patients who are unresponsive to or intolerant of available therapies. Programs that receive Fast Track Designation are entitled to more frequent interactions with the FDA on drug development plan, as well as eligibility for accelerated approval, priority review, and rolling review.

About Neuroendocrine Tumors (NET)

Neuroendocrine tumors form in cells that interact with the nervous system or in glands that produce hormones. They can originate in various parts of the body, most often in the gut or the lungs and can be benign or malignant. Neuroendocrine tumors are typically classified as pancreatic neuroendocrine tumors or non-pancreatic neuroendocrine tumors. According to cancer.net, it is estimated that more than 12,000 people in the United States are diagnosed with a NET each year. Importantly, neuroendocrine tumors are associated with a relatively long duration of survival compared to other tumors and as a result, there are approximately 175,000 people living with this diagnosis.

On October 3, 2022 Sysmex Corporation (HQ: Kobe, Japan; Chairman and CEO: Hisashi Ietsugu) and JCR Pharmaceuticals Co., Ltd. (HQ: Ashiya, Hyogo Prefecture; Chairman and President: Shin Ashida) reported that they have established a joint venture (hereafter "the joint venture") for carrying out research and development, manufacture and sales of cell-based regenerative medicine products including hematopoietic stem cells and other stem cells (Press release, Sysmex, OCT 3, 2022, View Source [SID1234621616]).

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In recent years, the significant potential of regenerative medicine and cell therapy have been established in particular in areas that have traditionally been difficult to address with conventional chemically synthesized low molecular weight drugs1 or biopharmaceuticals,2 such as the restoration of tissues and functions lost as a result of aging, illness, autoimmune diseases, or cancer. In particular, research and development on the therapeutic application of stem cells including hematopoietic stem cells, mesenchymal stem cells, and iPS cells have generated significant attention.

Since its foundation, Sysmex has provided network solutions using IoT (Internet of Things) and automated testing flows to improve the safety of healthcare professionals and for the optimization of operational efficiency in clinical laboratories. In addition, while providing quality control testing for companies which develop regenerative medicine products, Sysmex has conducted research and development related to new pre-transplant compatibility testing examining the patient’s immune response against the organ or tissue to be transplanted.

Since its inception, JCR has been engaged in the research, development, manufacturing and sales of pharmaceutical products using regenerative medicine, genetic engineering, and gene therapy technologies to advance therapies in the rare disease field. This is exemplified in the field of regenerative medicine, by the approval of TEMCELL HS Inj.,3 the first allogeneic regenerative medicine in Japan (Non-proprietary name: Human (allogeneic) bone marrow-derived mesenchymal stem cells) in February 2016 for the treatment of acute graft-versus-host disease (acute GVHD),4 a serious complication that develops after hematopoietic stem cell transplantation. In recent years, JCR has further streamlined and integrated its expertise around the establishment of groundbreaking medicines for the advancement of highly innovative medicines that could not be developed without such groundbreaking technologies.

In the joint venture, the two companies aim to realize the social implementation of regenerative medicine and cell therapy by integrating Sysmex’s expertise in quality control testing technology and knowledge of workflows efficiency using robotics technology, including IoT, with JCR’s expertise in developing, manufacturing and marketing regenerative medicine products. AlliedCel Corporation, which is the corporate name of the joint venture following prior discussions regarding the alliance both companies, was established on October 3, 2022. The joint venture will advance programs of the potential for technology development and commercialization, including the project currently being promoted by both companies using hematopoietic stem cell proliferation technology.

The name AlliedCel stands for the joint venture’s aspiration to integrate knowledge and expertise from a broad set of collaborators and stakeholders including business partners, patients and their families, with the united goal of unleashing the power of cells in supporting patients in their need for life-changing therapies. Through the research and development of regenerative medicine products using diverse cells such as stem cells, AlliedCel aims to provide appropriate treatment options to patients and improve their prognosis.

On October 3, 2022 Clovis Oncology, Inc. (NASDAQ: CLVS) reported positive top-line data from the Phase 3, open-label, multicenter, randomized TRITON3 trial demonstrating that Rubraca monotherapy treatment achieved the primary endpoint of significantly improved radiographic progression-free survival (rPFS) by independent radiology review (IRR) compared with the control group, which consisted of physician’s choice of docetaxel, abiraterone acetate, or enzalutamide (Press release, Clovis Oncology, OCT 3, 2022, View Source [SID1234621615]). Benefit was observed in both primary efficacy analyses of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC): first, those who had mutations in BRCA, as well as all patients randomized in the trial, inclusive of mutations in BRCA or ATM (the overall intent-to-treat population (ITT)). The safety profile of Rubraca observed in the TRITON3 study was consistent with Rubraca labelling.

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During the first quarter of 2023, the Company plans to submit a supplemental New Drug Application (sNDA) to the FDA for the BRCA subgroup of patients and intends to discuss with the FDA submitting for the broader ITT population.

"We believe that the positive results from TRITON3 further demonstrate the important role that Rubraca can play as a treatment option for men with metastatic castration-resistant prostate cancer associated with homologous recombination deficiency, and we look forward to submitting these data to the regulatory authorities in the US during Q1 2023. Not only does this provide a potential treatment option for eligible men with earlier stage disease, but it is the first and only PARP inhibitor that has demonstrated superior radiographic PFS compared to chemotherapy, which is today the standard of care for these patients," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "Most importantly, I would like to thank the patients, physicians, and our colleagues whose commitment to this trial made these results possible, which now offer the potential to make a difference in the lives of many men with advanced prostate cancer."

"Men with this type of metastatic prostate cancer want to get their genetically targeted therapy as early as possible, and this trial clearly shows the value of rucaparib as a treatment for these men," said Alan H. Bryce, MD, chair of the Division of Hematology and Medical Oncology at the Mayo Clinic and principal investigator of the TRITON3 trial. "A key point is that rucaparib can replace chemotherapy in this setting. The current standard of care for these men is chemotherapy with docetaxel, and rucaparib is the only PARP inhibitor which has beaten a docetaxel-containing control arm in a clinical trial."

"This trial demonstrates the potential for rucaparib to treat men with early-stage metastatic castration-resistant prostate cancer," said Karim Fizazi, MD, PhD, medical oncologist at Gustave Roussy, and a full professor in Oncology at the University of Paris-Saclay and principal investigator of the TRITON3 trial. "To my knowledge, this is the first time in two decades that a potential new treatment, rucaparib, has shown in a randomized controlled trial radiographic PFS efficacy over an investigator’s choice control arm that included docetaxel chemotherapy, a long-standing standard of care for men with metastatic castration-resistant prostate cancer, and this is excellent news for patients."

TRITON3 is a Phase 3, multicenter, open-label, randomized trial of Rubraca in patients with chemotherapy-naïve mCRPC. The study enrolled 405 patients with a mutation in BRCA or ATM who were randomized to Rubraca or the control group, which consisted of physician’s choice of docetaxel, abiraterone acetate, or enzalutamide. Approximately 55% of the patients in the control arm received docetaxel. The primary endpoint was rPFS by IRR, in patients with mutations in BRCA1, BRCA2or ATM. TRITON3 was designed as a Phase 3 trial to confirm and expand the efficacy data from TRITON2 in an earlier treatment setting against a relevant control arm.

Patients were required to have disease progression after treatment with one prior next-generation AR-targeted therapy (abiraterone acetate, enzalutamide, apalutamide or investigational agent), as well as a deleterious mutation in BRCA or ATM. Following a protocol amendment, patients were permitted to have received a qualifying AR-targeted therapy in either the hormone-sensitive or castration-resistant setting, and as a result, approximately 18% of patients in TRITON3 had received prior AR-targeted therapy in the metastatic hormone-sensitive setting only.

The primary efficacy analysis evaluated two prospectively defined molecular sub-groups in a step-down manner: 1) the BRCA subgroup, and 2) all patients randomized (ITT) in TRITON3, inclusive of those with BRCA or ATM mutations.

Following is a summary of the primary efficacy analyses of rPFS by independent radiologic review (IRR), the primary analysis of TRITON3.

Significant Improvement in rPFS in the BRCA Patient Population

The Rubraca arm (n=201) achieved statistical significance over the control arm (n=101) for the primary endpoint of rPFS with a hazard ratio of 0.50 (95% CI: 0.36-0.69). The median PFS for the population of patients with BRCA mutations treated with Rubraca was 11.2 months vs 6.4 months among those who received physician’s choice (p<0.0001).

Significant Improvement in rPFS in the ITT population, inclusive of those with BRCA or ATM mutations

Rubraca also showed statistical significance in all 405 patients randomized in TRITON3. The Rubraca arm (n=270) successfully achieved statistical significance over the control arm (n=135) for the primary endpoint of rPFS with a hazard ratio of 0.61 (95% CI: 0.47-0.80). The median PFS for all patients enrolled in TRITON3 and treated with Rubraca was 10.2 months vs 6.4 months among those who received physician’s choice (p=0.0003).

rPFS in Exploratory ATM Mutation Subgroup

In the exploratory subgroup of men with tumor ATM mutations (n=103), the hazard ratio for rPFS was 0.97 (95% CI: 0.59-1.52). Median rPFS in the Rubraca arm (n=69) was 8.1 months vs 6.8 months in the control arm (n=34) with a nominal p-value (p=0.8421).

Secondary Endpoint of Overall Survival Summary

The hazard ratio for the interim analysis of the secondary endpoint of overall survival (OS) in the BRCA subgroup and ITT population, which are not yet mature, favored Rubraca. The hazard ratio for OS in the exploratory subgroup of ATM, which is mature, favored the control arm. The 95% confidence intervals for these OS analyses included less than one for the exploratory endpoint ATM, signifying no statistical difference in outcomes between Rubraca and control.

Summary of TRITON3 Safety

The safety profile of Rubraca observed in TRITON3 was consistent with Rubraca labelling.The most common (≥5%) treatment-emergent grade 3 or higher adverse events (TEAEs) among all patients treated with Rubraca in the TRITON3 study were anemia/decreased hemoglobin (23.7%), neutropenia/decreased neutrophil count (7.4%), asthenia/fatigue (7.0%), thrombocytopenia/decreased platelet count (5.9%) and increased ALT/AST (5.2%). The discontinuation rate for TEAEs was 14.8% for Rubraca-treated patients and 21.5% for the control arm.

Clovis Oncology will submit an expanded description of the TRITON3 results for presentation in a scientific session at the Prostate Cancer Foundation Annual Scientific Retreat later this month and plans to submit additional data to a medical meeting in early 2023.

Rubraca is not currently approved in the chemotherapy-naïve mCRPC setting.

About the TRITON3 Clinical Trial

TRITON3 (NCT02975934) is a Phase 3, multicenter, open-label, randomized trial of Rubraca in patients with chemotherapy-naïve mCRPC. Patients with a mutation in BRCA or ATM were randomized to Rubraca or the control group, which consisted of physician’s choice of docetaxel, abiraterone acetate, or enzalutamide. The primary objective was efficacy, as analysed by independent radiology review (IRR) of radiographic progression-free survival (rPFS) in patients with mutations in BRCA1, BRCA2 or ATM. TRITON3 was designed as a Phase 3 trial to confirm and expand the efficacy data from TRITON2 in an earlier treatment setting against a relevant control arm.

About Prostate Cancer

The American Cancer Society estimates that approximately 268,000 men in the US will be diagnosed with prostate cancer in 2022, and the GLOBOCAN Cancer Fact Sheets estimated that approximately 473,000 men in Europe were diagnosed with prostate cancer in 2020. Castrate-resistant prostate cancer has a high likelihood of developing metastases. Metastatic castrate-resistant prostate cancer (mCRPC) is an incurable disease, usually associated with poor prognosis.i Approximately 43,000 men in the US were expected to be diagnosed with mCRPC in 2020.ii According to the National Cancer Institute, the five-year survival rate for mCRPC is approximately 30%. BRCA or ATM mutations have been detected in approximately 19% of patients with mCRPC according to articles published in JCO Precision Oncology in 2017 and in Clinical Cancer Research in 2021. These molecular markers may be used to select patients for treatment with a PARP inhibitor.iii

About Rubraca (rucaparib)

Rubraca 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.

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) have occurred 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. In TRITON2, MDS/AML was not observed in patients with mCRPC (n=209) regardless of homologous recombination deficiency (HRD) mutation.

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 TRITON2 (≥ 20%; Grade 1-4) were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

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.