On December 11, 2019 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported that results from an ongoing Phase II clinical trial of Puma’s drug neratinib are being presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas (Press release, Puma Biotechnology, DEC 11, 2019, View Source [SID1234552255]). The presentation entitled, "Neratinib + trastuzumab + fulvestrant for HER2-mutant, hormone receptor-positive, metastatic breast cancer: updated results from the phase 2 SUMMIT ‘basket’ trial," are being presented at a poster Session by Hans Wildiers, M.D., Ph.D., University Hospitals Leuven, Belgium, an investigator of the trial. A copy of this poster presentation is available on the Puma website

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Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy and is marketed in the United States as NERLYNX (neratinib) tablets. NERLYNX was granted marketing authorization by the European Commission for the extended adjuvant treatment of hormone receptor-positive HER2-positive early stage breast cancer in August 2018.

The Phase II SUMMIT basket trial is an open-label, multicenter, multinational study to evaluate the safety and efficacy of neratinib administered daily to patients who have solid tumors with activating HER2 or HER3 mutations. In the HER2-mutant, HR-positive breast cancer cohort, 28 patients received 240 mg of neratinib daily in combination with trastuzumab and fulvestrant. In this cohort, patients had received a median of 4 prior lines of therapy in the metastatic setting (range 0-10 prior regimens) before entering the trial. All patients had been previously treated with an endocrine agent prior to entering the study, including 17 patients (61%) who had received prior fulvestrant. Further, 15 patients (54%) received prior cyclin-dependent kinase 4/6 (CDK4/6) -inhibitor therapy. Twenty-one patients (75%) had received prior chemotherapy.

The interim efficacy summary of the breast cohort that received neratinib in combination with trastuzumab and fulvestrant showed that for the 17 efficacy evaluable patients, 9 patients (53%) experienced a confirmed objective response, all of which were classified as partial responses, and 10 patients (59%) experienced clinical benefit (clinical benefit is defined as confirmed complete response or partial response or stable disease for at least 24 weeks). The median duration of response has not been reached and the median progression-free survival was 9.8 months. At the time of data cut-off, five patients continued to receive treatment.

The safety profile observed in patients treated with the combination of neratinib plus trastuzumab plus fulvestrant in the SUMMIT study was consistent with that observed previously in metastatic patients with HER2 amplified tumors. All patients received anti-diarrheal prophylaxis with loperamide alone. The interim safety results of the study showed that the most frequently observed adverse event was diarrhea. For the 28 safety evaluable patients enrolled in this cohort, 10 patients (36%) reported grade 3 diarrhea. The median duration of grade 3 diarrhea for those patients was 5.5 days. No patient permanently discontinued neratinib due to diarrhea.

Prof. Dr. Hans Wildiers said, "The combination of neratinib plus trastuzumab plus fulvestrant therapy demonstrates encouraging clinical activity with durable responses in this heavily pretreated metastatic breast cancer patient population with activating HER2 mutations and hormone receptor-positive disease. We look forward to continuing to enroll this cohort of SUMMIT."

Alan H. Auerbach, CEO and President of Puma Biotechnology, added, "We are very pleased with the activity seen with neratinib in combination with trastuzumab and fulvestrant in this cohort of patients with HER2-mutated breast cancer. We are in the process of expanding this HR-positive breast cancer cohort in SUMMIT with the intent of using this data to support future registration. We look forward to enrolling additional patients into this HR-positive breast cancer cohort in order to generate the additional data required to support approval of this combination therapy."

On December 11, 2019 NeoImmuneTech, Inc., a clinical-stage T cell-focused biopharmaceutical company, reported it has entered into a clinical collaboration agreement with Merck, known as MSD outside of the United States and Canada, through a subsidiary, to evaluate the combination of NeoImmuneTech’s Hyleukin-7 (NT-I7) and Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in a basket study in patients with relapsed/refractory (R/R) advanced solid tumors (Press release, NeoImmuneTech, DEC 11, 2019, View Source [SID1234552272]).

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The goal of the Phase 1b/2a study is to establish a recommended dosing regimen and explore the preliminary anti-tumor activity of the combination in patients with both checkpoint inhibitor (CPI)-treated and CPI-naïve R/R tumors. The results of this study will be used to further clinical development of this combination in select tumor types.

"Although immunotherapy has become the new paradigm in cancer treatment, the majority of patients fail to respond. For tumors that are considered non-responsive to CPIs, such as microsatellite stable colorectal cancer and pancreatic cancer, the response to single-agent CPI has been low," said NgocDiep Le, M.D., Ph.D., NIT’s Executive VP and Chief Medical Officer. "Since immunotherapies rely heavily on the anti-tumor activity of T cells, Hyleukin-7’s demonstrated ability to increase multiple T-cell subsets potentially enhances the breadth and depth of the response to CPIs such as KEYTRUDA."

Se Hwan Yang, Ph.D., NIT’s Co-President and Chief Executive Officer, added: "We are excited to partner with Merck in our endeavor to provide new treatment options for patients whose tumors do not respond to CPIs or have progressed after CPI treatment. This combination approach could open the door to expanding the use of immunotherapy to these patients and ultimately improve clinical outcomes."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., USA.

About Hyleukin-7
Hyleukin-7 (NT-I7), the only clinical-stage long-acting human IL-7, is uniquely positioned to address unmet medical needs in immuno-oncology. IL-7 is a fundamental cytokine for T-cell development and for sustaining immune response to chronic antigens (as in cancer). Hyleukin-7’s favorable PK/PD and safety profiles make it an ideal combination partner for immunotherapy standard of care (SOC) such as Checkpoint Inhibitor and CAR-T therapies. Hyleukin-7 is being studied in multiple clinical trials in solid tumors, and being planned for testing in hematologic malignancies, additional solid tumors and other immunology-focused indications.

On December 11, 2019 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases, reported financial results for the third quarter ended September 30, 2019 and provided an update on recent operational and business progress (Press release, RAPT Therapeutics, DEC 11, 2019, View Source [SID1234552256]).

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"We are pleased to report significant progress as a public company following our initial public offering," said Brian Wong, M.D., Ph.D., President and CEO of RAPT Therapeutics. "This includes clinical and operational advancement of our two lead compounds, FLX475 for oncology and RPT193 for allergic inflammatory disease. We recently announced a collaboration with Hanmi for FLX475 in Asia, a region with a high prevalence of ‘charged’ tumors. As we look toward 2020, we expect to report clinical proof of concept data for each program as we reach milestone events in our ongoing clinical trials."

Recent Highlights

Signed a license and collaboration agreement with Hanmi Pharmaceutical Co., LTD for the development and commercialization of FLX475 in Korea and China, including Taiwan and Hong Kong. RAPT will receive $10 million in an upfront payment and near-term milestone payment, and will receive up to $48 million in success-based development milestones and up to $60 million in potential sales milestones, as well as double-digit royalties on any future sales of FLX475 in the specified territories. In addition to leveraging its clinical trial infrastructure in Korea and China to augment RAPT’s ongoing Phase 1/2 clinical study of FLX475, Hanmi will conduct a Phase 2 clinical trial in Korea and China to evaluate FLX475 in patients with gastric cancer.

Continued enrolling patients with "charged" tumors in a Phase 1/2 study of FLX475 as a monotherapy and in combination with pembrolizumab.

Initiated a first-in-human Phase 1 study of RPT193, a CCR4 antagonist to treat allergic inflammatory diseases, including atopic dermatitis.

Completed its initial public offering (IPO), raising $33.8 million in net proceeds, which includes the underwriters’ exercise of their overallotment option to purchase additional shares at the IPO price. The Company’s stock commenced trading on the Nasdaq Global Select Market under the ticker symbol "RAPT."

Appointed Rodney Young as Chief Financial Officer.

Appointed Wendye Robbins, M.D., President and CEO of Blade Therapeutics, and Mary Ann Gray, Ph.D., President of Gray Strategic Advisors, LLC, to the Board of Directors.

Financial Results for the Third Quarter and Nine Months Ended September 30, 2019

Third Quarter ended September 30, 2019

Net loss for the third quarter of 2019 was $10.0 million, compared to $10.3 million for the third quarter of 2018.

Research and development expenses for the third quarter of 2019 were $8.6 million, compared to $9.2 million for the same period in 2018. The decrease was primarily due to decreases in costs relating to the clinical development of FLX475, outsourced research and development, and lab supplies, offset by increases in costs relating to the clinical development of RPT193 and personnel.

General and administrative expenses for the third quarter of 2019 were $1.7 million, compared to $1.4 million for the same period in 2018.

Nine Months Ended September 30, 2019

Net loss for the nine months ended September 30, 2019 was $29.8 million, compared to $26.7 million for the same period in 2018.

Research and development expenses for the nine months ended September 30, 2019 were $24.7 million, compared to $23.4 million for the same period in 2018. The increase was primarily due to increases in costs relating to the clinical development of RPT193, facilities and personnel, offset by decreases in costs relating to the clinical development of FLX475, lab supplies and outsourced research and development.

General and administrative expenses for the nine months ended September 30, 2019 were $6.1 million, compared to $3.9 million for the same period in 2018. The increase was primarily due to increases in professional service fees related to the Company’s preparation of its initial public offering.

As of September 30, 2019, the Company had cash and cash equivalents of $48.3 million. The Company completed its initial public offering on November 4, 2019 and received net proceeds of approximately $33.8 million, which includes the underwriters’ exercise of the overallotment option.

On December 11, 2019 IASO Biotherapeutics (IASO Bio), a clinical-stage biotechnology company advancing the development of innovative therapies for cancer, reported that had the latest clinical data presented on their potential best-in-class therapy at the "Efficacy and Safety of Fully Human BCMA Targeting CAR T Cell Therapy in Relapsed Refractory Multiple Myeloma" session during the prestigious 61st Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting & Exposition, December 7-10 in Orlando, FL (Abstract #582) (Press release, IASO BioMed, DEC 11, 2019, View Source [SID1234552273]).

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In an IIT study conducted by Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, the oral presentation highlighted the impressive safety, efficacy and persistence of CT103A, an anti-BCMA CAR-T for the treatment of Relapsed/Refractory Multiple Myeloma. With 17 of the 18 patients evaluable, the objective response rate (ORR) was 100%. In addition, 70.6% of patients achieved a best response of stringent complete or complete response (sCR/CR), and 88.2% achieved a best response of very good partial response (VGPR) or better. CRS occurred in 17 of 18 patients (Grade 1&2- 72.2% (13), Grade 3- 16.7% (3), Grade 4- 5.6% (1)), but was generally manageable with no neurotoxicity. At the lowest dose (1 x106 cells/kg), CT103A still maintained 100% ORR, with 78% of these patients achieving a best response of very good partial response (VGPR) or better. As well, toxicity was manageable with 88% of these patients experiencing grade 2 CRS or less.

In addition, 4 patients participating in the study had relapsed from a prior murine CAR-T infusion. Their response, and the overall performance, suggests that CT103A may also provide patients, having relapsed from a prior CAR-T, a potential first-line treatment option

"Having presented at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) earlier this year, our presence at ASH (Free ASH Whitepaper) marks the end of a very exciting year for IASO BIO. We are very happy to see the prolonged patient response to this therapy and look forward to starting our phase II clinical trial early in the new year," said Hu Guang, Ph.D., Director of R&D at IASO BIO. "By applying highly innovative science in our pre-clinical programs, we believe our pipeline has potential to bring us closer to addressing critical unmet needs, not just for patients, but for the healthcare professionals that treat them."

Multiple Myeloma is a deadly blood cancer that often infiltrates the bone marrow causing anemia, kidney failure, immune problems and bone fractures. With a global annual incidence rate of 2/100,000 persons, it is one of the most commonly diagnosed blood cancers, second only to non-Hodgkin lymphoma.

This past September CT103A received IND approval for Ib/II chimeric protocol by the National Medical Products Association (NMPA), and phase II clinical trials are expected to begin in early 2020.

About Relapsed/Refractory Multiple Myeloma

For newly treated patients with multiple myeloma, common first-line treatment drugs include proteasome inhibitors, immunoregulatory drugs and alkane agents. For most patients, the commonly used first-line treatment can stabilize the patient’s condition for 3-5 years, but a small number of patients show primary drug resistance at the time of initial treatment, and the disease cannot be effectively controlled. Relapse patients are those who have a reoccurrence after complete remission of the disease. Refractory patients are those with primary drug resistance or those who have finished first-line treatment and do not achieve remission, or patients whose disease progress within 60 days after achieving minimal response. With effective treatment, the majority of patients will inevitably enter the stage of relapse and refractory after 3-5 years of disease stabilization. For these patients, the overall effective rate of existing second-line treatment is about 40% to 70%, with short remission time.

About CT103A

CT103A is an innovative therapy co-developed by IASO BIO and Innovent. Previous studies indicate patients with relapsed/refractory multiple myeloma (RRMM) who received high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re-infusion of CAR-T cells is not effective. To solve this dilemma, CT103A has been developed. A lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3z activation domains. Based on strict selection and screening, utilizing a proprietary in-house optimization platform, the construct of the CT103A CAR-T is potent and persistent.

On December 11, 2019 Ionis Pharmaceuticals, Inc. (the "Company") reported that it entered into separate privately negotiated exchange and/or subscription agreements with certain new investors and certain of the holders of its 1.00% Convertible Senior Notes due 2021 (the "2021 Notes") to exchange $375.6 million in aggregate principal amount of the Company’s 2021 Notes (the "Exchange Transactions") for $439.4 million in aggregate principal amount of the Company’s 0.125% Convertible Senior Notes due 2024 (the "Notes"), and to issue and sell an additional $109.5 million in aggregate principal amount of the Notes (the "Subscription Transactions" and, together with the Exchange Transactions, the "Transactions") (Filing, 8-K, Ionis Pharmaceuticals, DEC 11, 2019, View Source [SID1234552570]).

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On December 19, 2019 and December 20, 2019, the Company issued a total of $548.8 million aggregate principal amount of Notes in the Transactions. The Notes are general unsecured obligations of the Company and bear interest at a fixed rate of 0.125% per year, payable semiannually in arrears on June 15 and December 15 of each year, beginning on June 15, 2020. The Notes are convertible under certain circumstances and may be settled as described below. The conversion rate is initially 12.0075 shares of the Company’s common stock per $1,000 principal amount of Notes (equivalent to an initial conversion price of approximately $83.28 per share of the Company’s common stock). The conversion rate and the corresponding conversion price will be subject to adjustment in some events but will not be adjusted for any accrued and unpaid interest. In addition, if certain corporate events occur prior to the maturity date, the Company will increase the conversion rate for a holder who elects to convert its Notes in connection with such a corporate event in certain circumstances. The Company may not redeem the Notes prior to maturity, and no sinking fund is provided for the Notes. The Notes will mature on December 15, 2024, unless earlier converted or purchased.

The Company did not receive any cash proceeds from the Exchange Transactions. In exchange for issuing the Notes pursuant to the Exchange Transactions, the Company received and cancelled the exchanged 2021 Notes. The Company estimates the net proceeds from the Subscription Transactions were approximately $99.2 million after deducting estimated offering expenses for the Transactions. The Company used a portion of the net cash proceeds from the Subscription Transactions to pay the costs of the previously disclosed convertible note hedge transactions and intends to use the remaining net cash proceeds for general corporate purposes.

Indenture

The Company issued the Notes pursuant to an indenture, dated as of December 19, 2019 (the "Indenture"), by and between the Company and U.S. Bank National Association, as trustee.

Holders of the Notes may convert their Notes at their option at any time prior to the close of business on the business day immediately preceding August 1, 2024 only under the following circumstances: (1) during any calendar quarter commencing after March 31, 2020 (and only during such calendar quarter), if the last reported sale price of the Company’s common stock for at least 20 trading days (whether or not consecutive) during a period of 30 consecutive trading days ending on the last trading day of the immediately preceding calendar quarter is greater than or equal to 130% of the conversion price on each applicable trading day; (2) during the five business day period after any five consecutive trading day period (the "measurement period") in which the trading price per $1,000 principal amount of Notes for each trading day of the measurement period was less than 98% of the product of the last reported sale price of the Company’s common stock and the conversion rate on each such trading day; or (3) upon the occurrence of specified corporate events. On or after August 1, 2024 until the close of business on the second scheduled trading day preceding the maturity date, holders of the Notes may convert their Notes at their option at the conversion rate then in effect at any time irrespective of the foregoing conditions. The Company will settle conversions of Notes by paying and/or delivering, as the case may be, cash, shares of the Company’s common stock, or a combination of cash and shares of the Company’s common stock, at its election, as described in the Indenture.

The Company may not redeem the Notes prior to maturity and no ‘‘sinking fund’’ is provided for the Notes, which means that the Company is not required to redeem or retire the Notes periodically.

If the Company undergoes a fundamental change (as defined in the Indenture), subject to certain conditions, holders of the Notes may require the Company to purchase for cash all or part of their Notes in principal amounts of $1,000 or a multiple thereof, at a purchase price equal to 100% of the principal amount of the Notes to be purchased, plus accrued and unpaid interest to, but excluding, the fundamental change purchase date.

The Notes are the Company’s general unsecured obligations and rank senior in right of payment to any of the Company’s indebtedness that is expressly subordinated in right of payment to the Notes; equal in right of payment with any of the Company’s liabilities that are not so subordinated (including the 2021 Notes); effectively junior in right of payment to any of the Company’s secured indebtedness to the extent of the value of the assets securing such indebtedness; and structurally junior to all indebtedness and other liabilities (including trade payables) of the Company’s subsidiaries.

The events of default, which may result in the acceleration of the maturity of the Notes, include, among other things:

failure to pay interest on the Notes when due and the continuance of such default for a period of 30 days;

failure to pay the principal on the Notes when due;

failure to comply with the Company’s obligation to convert the Notes in accordance with the Indenture upon exercise of a holder’s conversion right and such failure continues for a period of three (3) business days;

failure to provide timely notice of a fundamental change or a specified corporate transaction;

failure by the Company to comply with its obligations under the Notes or the Indenture for a period of 60 days after notice if given in accordance with the Indenture;

certain defaults under loan agreements or other instruments (other than the Indenture) evidencing indebtedness for borrowed money of the Company or any significant subsidiary of the Company in excess of $100 million; and

certain events of bankruptcy or insolvency involving the Company or any significant subsidiary of the Company.