On June 23, 2020 Poseida Therapeutics reported that it filed a new preliminary prospectus for a $115 million initial public offering (IPO) (Press release, BioSpace, JUN 23, 2020, View Source [SID1234561403]). The company is focused on developing cell and gene therapies based on a proprietary DNA modification, gene editing and delivery technology.

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Initially, Poseida had been aiming for an IPO in January of last year. However, the company changed its plans after it raised $142 million in a Series C funding round. It received a $75 million equity investment from Novartis Pharma AG, and also had support from new investors including Aisling Capital Management, Pentwater Capital Management and Perceptive Advisors.

"We welcome the support and investment from Novartis, a leader in the cell and gene therapy field," said Eric Ostertag M.D., Ph.D., chief executive officer of Poseida, following the closure of the Series C financing round. "They are joined by an impressive group of new investors whose commitment enables us to accelerate the pursuit of our bold vision to create gene therapy product candidates that could result in single-treatment cures for numerous oncologic indications and orphan genetic diseases, with an initial focus on chimeric antigen receptor T cell (CAR-T) therapies."

Poseida has several CAR-T product candidates, which are manufactured utilizing its non-viral DNA modification system, which results in a high percentage of stem cell memory cells (Tscm). Tscm cells are the only T cell that is self-renewing and long-lived, which can translate into more efficacious, less toxic and durable product candidates.

Some of Poseida’s product candidates include P-BCMA-101, an autologous CAR-T therapy for the treatment of relapsed/refractory multiple myeloma; P-PSMA-101, an autologous CAR-T product candidate targeting PSMA-specific cancer cells in castrate resistant prostate cancer; and P-MUC1C-101, an autologous CAR-T product candidate in late-stage preclinical development for numerous solid tumor indications.

Poseida announced in May 2019 that P-BCMA-101 had received orphan drug designation from the U.S. Food and Drug Administration (FDA) for the treatment of relapsed and/or refractory multiple myeloma.

"FDA orphan designation is an important regulatory milestone in the continued development and commercialization of P-BCMA-101," said Ostertag, at the time of the announcement. "P-BCMA-101 has demonstrated outstanding potency, with strikingly low rates of toxicity in our phase 1 clinical trial. In fact, the FDA has approved fully outpatient dosing in our Phase 2 trial starting in the second quarter of 2019."

In May of this year, Poseida also announced that it had made progress with P-PSMA-101 by dosing its first patient with the candidate in a Phase 1 clinical trial, evaluating the autologous CAR-T therapeutic product for the treatment of metastatic castration-resistant prostate cancer. The goal of the Phase 1 study is to determine which dose is best for patients with the fewest side effects. P-PSMA-101 is designed to target prostate-specific membrane antigen, which is expressed on metastatic castration-resistant prostate cancer cells.

"Extending our gene engineering technology to solid tumors represents the next opportunity in oncology where we believe our proprietary platforms and approach have advantages over others in the space," said Ostertag. "Our platform technologies, which include the piggyBac DNA Modification System and Cas-CLOVER site-specific gene editing system, are driving our diverse pipeline of next-generation CAR-T treatments for hematologic and solid tumors, as well as gene therapies addressing rare diseases."

Poseida remains dedicated to engineering a wide array of next-generation cell and gene therapeutics using its various platform technologies.

On June 23, 2020 Gilead Sciences, Inc. (Nasdaq: GILD) reported that for $275 million the company will acquire a 49.9 percent equity interest in Pionyr Immunotherapeutics Inc., a privately held company developing first-in-class cancer immunotherapies, and an exclusive option to purchase the remainder of Pionyr (Press release, Gilead Sciences, JUN 23, 2020, View Source [SID1234561402]). Under the agreement, Pionyr’s shareholders may receive up to an additional $1.47 billion in option exercise fees and future milestone payments.

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Pionyr’s Myeloid Tuning therapies have the potential to treat patients who currently do not benefit from checkpoint inhibitor therapies. PY314 and PY159 have demonstrated preclinical efficacy, suggesting potential in solid tumors in combination with established anti-PD(L)-1 agents. Pionyr plans to file investigational new drug (IND) applications with the U.S. Food and Drug Administration for both PY314 and PY159 in the third quarter of this year. Pending Phase 1b results from either candidate – or sooner if Gilead chooses – Gilead can exercise its exclusive option to acquire the remainder of Pionyr.

"Pionyr is pursuing promising, novel biology in the field of immuno-oncology," said Daniel O’Day, Chairman and Chief Executive Officer, Gilead Sciences. "The agreement represents important progress as we continue to build out Gilead’s presence in immuno-oncology with innovative and complementary approaches. We look forward to seeing the programs advance with the goal of developing new therapies that will improve the treatment of cancer."

"This agreement underscores the value of our myeloid tuning platform and the potential of our pipeline of antibody therapeutics designed to turbocharge the immune system within the tumor microenvironment," said Steven P. James, President and Chief Executive Officer, Pionyr. "PY314 and PY159 are first-in-class antibodies designed to remove or reprogram, respectively, the immune suppressive cells in the tumor microenvironment and thereby enhance anti-tumor immunity. We are grateful that Gilead has acknowledged the promise of this transformational approach to potentially benefit patients across a range of solid tumors."

Terms of the Agreement

Under the terms of the agreement, Pionyr’s shareholders will receive $275 million upon closing. Gilead will receive 49.9 percent of the common stock of Pionyr and an exclusive option to purchase the remaining equity. Gilead may exercise its exclusive option upon completion of Phase 1b studies for PY314 and PY159, or at an earlier time if Gilead chooses to do so, for a $315 million option exercise fee and up to $1.15 billion in potential future milestone payments. In addition, Gilead will provide Pionyr with additional funding for the PY314 and PY159 clinical programs, as well as ongoing research and development programs.

The transaction is subject to customary closing conditions and is expected to close shortly.

Gilead will have the right to nominate one individual to Pionyr’s Board of Directors upon closing of the transaction. In addition, Gilead and the other stockholders of Pionyr will jointly select and nominate one independent individual to Pionyr’s Board of Directors.

BofA Securities is acting as financial advisor to Gilead. Centerview Partners LLC is acting as financial advisor to Pionyr.

About Myeloid Tuning

Pionyr has developed a research approach called Myeloid Tuning, which is designed to rebalance the tumor microenvironment (TME) to promote anti-tumor immunity. Myeloid cells are a family of cell types that play an important role in both the activation and in the suppression of immune response to cancer. PY314 targets TREM2, a protein commonly found on the surface of a certain type of immunosuppressive, pro-tumor myeloid cells. PY314 is designed to selectively deplete these cells, resulting in a rebalancing of the tumor microenvironment that favors anti-tumor immunity. PY159 targets TREM1, a protein that is expressed on multiple immunosuppressive myeloid cells such as macrophages, neutrophils and myeloid derived suppressor cells. PY159 is designed to reprogram these immunosuppressive cells to instead stimulate a pro-inflammatory, anti-tumor immune response

On June 23, 2020 Thermo Fisher Scientific and Daiichi Sankyo reported that they have expanded their partnership by signing a new agreement to co-develop a companion diagnostic (CDx) that will utilize Thermo Fisher’s next-generation sequencing (NGS)-based Oncomine Dx Target Test (Press release, Thermo Fisher Scientific, JUN 23, 2020, https://www.prnewswire.com/news-releases/thermo-fisher-scientific-and-daiichi-sankyo-to-co-develop-global-companion-diagnostic-for-patients-with-non-small-cell-lung-cancer-301081575.html [SID1234561401]). The CDx will be designed to identify non-small cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) mutations who may be eligible for Enhertu, a HER2 directed antibody drug conjugate (ADC), which is currently in global phase 2 development for HER2 mutated or HER2 overexpressing NSCLC.

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Enhertu has demonstrated a strong response rate in patients with HER2 positive metastatic breast cancer and preliminary results show a similar response in patients with metastatic NSCLC with HER2 mutations.1-2 HER2 mutations have long been implicated in breast cancers, but they are considered a rare event in NSCLC. Recent studies have found that HER2 mutations are the key drivers in about 1-3 percent of NSCLC cases.3

Under the terms of the agreement, Thermo Fisher will retain rights to commercialize the test globally and will seek approval from regulatory agencies. The announcement follows a 2018 agreement between the companies to expand the clinical utility of the test in support of clinical trials and drug development programs at Daiichi Sankyo.

The Oncomine Dx Target Test is the first targeted NGS in vitro diagnostic test approved by the U.S. Food and Drug Administration (FDA) for NSCLC. It is designed to evaluate multiple biomarkers associated with cancer and identify patients who are eligible for multiple FDA-approved targeted therapies using a single sample with results available in days.

"Our latest partnership with Daiichi Sankyo is focused on helping to solve an unmet medical need for a growing number of patients with HER2-mutated non-small cell lung cancer," said Garret Hampton, president of clinical next-generation sequencing and oncology at Thermo Fisher Scientific. "This agreement underscores our continued commitment to working with global pharmaceutical partners to efficiently identify more patients who may benefit from the latest targeted therapies in their drug pipelines."

U.S. FDA-Approved Indication for ENHERTU
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.
Contraindications
None.

WARNINGS AND PRECAUTIONS

Interstitial Lung Disease / Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg prednisolone or equivalent). Upon improvement, follow by gradual taper (e.g., 4 weeks).

Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, a decrease in neutrophil count was reported in 30% of patients and 16% had Grade 3 or 4 events. Median time to first onset was 1.4 months (range: 0.3 to 18.2). Febrile neutropenia was reported in 1.7% of patients.

Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. Based on the severity of neutropenia, ENHERTU may require dose interruption or reduction. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109 /L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level.

Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. Permanently discontinue ENHERTU if LVEF of <40% or absolute decrease from baseline of >20% is confirmed. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure.

Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

Adverse Reactions
The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

The most common adverse reactions (frequency ≥20%) were nausea (79%), fatigue (59%), vomiting (47%), alopecia (46%), constipation (35%), decreased appetite (32%), anemia (31%), neutropenia (29%), diarrhea (29%), leukopenia (22%), cough (20%), and thrombocytopenia (20%).

Use in Specific Populations

Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU.
Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (53%) as compared to younger patients (42%).
Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.

On June 23, 2020 Repare Therapeutics Inc. (Nasdaq: RPTX), a leading precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics, reported the closing of its previously announced upsized initial public offering of 12,650,000 of its common shares, including the exercise in full of the underwriters’ option to purchase up to an additional 1,650,000 common shares, at a public offering price of $20.00 per share (Press release, Repare Therapeutics, JUN 23, 2020, View Source [SID1234561400]). The gross proceeds to Repare, before deducting underwriting commissions and offering expenses, were $253.0 million. All of the common shares were offered by Repare.

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Repare’s common shares are listed on the Nasdaq Global Select Market under the ticker symbol "RPTX."

Morgan Stanley, Goldman Sachs & Co. LLC, Cowen and Piper Sandler & Co. acted as joint book-running managers for the offering.

The shares were offered by Repare pursuant to a registration statement that was declared effective by the U.S. Securities and Exchange Commission ("SEC") on June 18, 2020. A prospectus relating to and describing the terms of the offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov.

The offering of these shares was made only by means of a prospectus. Copies of the final prospectus relating to this offering may be obtained from Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, New York 10014; Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone: 1-866-471-2526 or by emailing [email protected]; Cowen and Company, LLC c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY, 11717, Attn: Prospectus Department, by email at [email protected] or by telephone at (833) 297-2926; or Piper Sandler & Co., Attn: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, by telephone at 800-747-3924 or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of Repare’s common shares in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state or jurisdiction.

On June 23, 2020 Forma Therapeutics Holdings, Inc. (Nasdaq: FMTX), a clinical-stage biopharmaceutical company focused on rare hematologic diseases and cancers, reported the closing of its initial public offering of 15,964,704 shares of common stock, including the exercise in full by the underwriters of their option to purchase up to 2,082,352 additional shares of common stock, at a public offering price of $20.00 per share (Press release, Forma Therapeutics, JUN 23, 2020, View Source [SID1234561399]). The aggregate gross proceeds to Forma from the offering were approximately $319.3 million, before deducting underwriting discounts and commissions and other offering expenses. All of the shares in the offering were offered by Forma.

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Jefferies, SVB Leerink and Credit Suisse acted as joint book-running managers for the offering.

Registration statements relating to these securities have been filed with the Securities and Exchange Commission ("SEC") and became effective on June 18, 2020. The offering was made only by means of a prospectus. Copies of the final prospectus relating to this offering may be obtained from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by telephone at (877) 821-7388, or by email at [email protected]; SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at (800) 808-7525, ext. 6218, or by email at [email protected]; or Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, 6933 Louis Stephens Drive, Morrisville, NC 27560, by telephone at (800) 221-1037, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.