On September 27, 2019, Rigel Pharmaceuticals, Inc., a Delaware corporation (the "Company") reported that it entered into a Credit and Security Agreement, dated as of September 27, 2019 (the "Closing Date") by and among the Company, the lenders party thereto from time to time and MidCap Financial Trust, as administrative agent and collateral agent ("Agent") (the "Term Loan Credit Agreement"), which provides for a $60 million term loan facility (Filing, 8-K, Rigel, SEP 27, 2019, View Source [SID1234552181]). The Term Loan Credit Agreement provides for (i) on the Closing Date, $10.0 million aggregate principal amount of term loans, (ii) at the Company’s option, until December 31, 2020, an additional $10.0 million term loan facility, (iii) at the Company’s option, until March 31, 2021, an additional $20.0 million term loan facility subject to the satisfaction of certain conditions ("Tranche Three") and (iv) at the Company’s option, until March 31, 2022, an additional $20.0 million term loan facility subject to the satisfaction of certain conditions ("Tranche 4") (collectively, the "Term Loans"). The Company used the proceeds of the Term Loans for general corporate purposes

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The obligations under the Term Loan Credit Agreement are secured by a perfected security interest in all of the Company’s assets except for intellectual property and certain other customary excluded property pursuant to the terms of the Term Loan Credit Agreement.

The Term Loans are subject to an origination fee of 0.25% of each funded tranche of Term Loans. The Company will pay the Agent an annual administrative fee of 0.25% of the amount borrowed under the Term Loans, payable annually. The Term Loans may be prepaid in full or in part through September 27, 2020 with payment of a 2.5% prepayment premium, after which they may be prepaid in full or in part through September 27, 2021 with payment of a 1.5% prepayment premium, after which they may be prepaid in full or in part through September 27, 2022 with payment of a 1.0% prepayment premium, after which they may be prepaid in full or in part with no prepayment premium. An additional 2.5% of the amount of Terms Loans advanced by the lenders will be due upon prepayment or repayment of the Term Loans in full.

The interest rate applicable to the Term Loans is LIBOR plus 5.65%, subject to a LIBOR floor of 1.50%. Commencing October 1, 2019, the Company initially will make interest-only payments for 24 months, followed by 36 months of amortization payments. The interest-only period will be extended to 36 months and again to 48 months upon the satisfaction of certain conditions set forth in the Term Loan Credit Agreement. All unpaid principal and accrued interest is due and payable in full no later than September 1, 2024.

The Term Loan Credit Agreement requires that the Company (i) upon both of (x) the draw of Tranche 3 or Tranche 4 and (y) cash falling below 1.25x Term Loans outstanding, maintain U.S. Tavalisse Net Revenue (as defined in the Term Loan Credit Agreement) in amounts set forth in the Term Loan Credit Agreement and (ii) upon the draw of Tranche 3 or Tranche 4, maintain cash and cash equivalents of at least $10.0 million. The Term Loan Credit Agreement also contains customary representations and warranties and customary affirmative and negative covenants, including, among other things, restrictions on indebtedness, liens, investments, mergers, dispositions, prepayment of other indebtedness and dividends and other distributions.

Events of default under the Term Loan Credit Agreement include: (i) failure by the Company to timely make payments due under the Term Loan Credit Agreement; (ii) material misrepresentations or misstatements in any representation or warranty by the Company when made; (iii) failure by the Company or its subsidiaries to comply with the covenants under the Term Loan Credit Agreement and other related agreements; (iv) certain defaults under a specified amount of other indebtedness of the Company or its subsidiaries; (v) insolvency or bankruptcy-related events with respect to the Company or any of its subsidiaries; (vi) certain undischarged judgments against the Company or its subsidiaries; (vii) certain ERISA-related events with respect to the Company or its subsidiaries above a specified amount; (viii) certain security interests or liens under the loan documents ceasing to be, or being asserted by the Company not to be, in full force and effect; (ix) the institution of criminal proceedings against the Company; (x) an event of default under the guarantee of the obligations under the Term Loan Credit Agreement; (xi) the prepayment of any subordinated debt other than as specifically permitted by the terms of such subordination; (xii) the occurrence of a Material Adverse Change (as defined in the Term Loan Credit Agreement); (xiii) certain adverse actions by the FDA or DEA with respect to certain products or which could be reasonably expected to result in a Material Adverse Change (as defined in the Term Loan Credit Agreement); (xiv) a default or material breach under certain specified material contracts and (xv) any loan document ceasing to be, or any challenge or assertion by the Company that such loan document is not, in full force and effect. If one or more events of default occurs and continues beyond any applicable cure period, the Agent may, with the consent of the lenders holding a majority of the loans and commitments under the facilities, or will, at the request of such lenders, terminate the commitments of the lenders to make further loans and declare all of the obligations of the Company under the Term Loan Credit Agreement to be immediately due and payable.

On September 27, 2019 Amgen (NASDAQ: AMGN) reported new data from the ongoing Phase 1 study evaluating AMG 510 in patients with previously treated KRAS G12C-mutant solid tumors (Press release, Amgen, SEP 27, 2019, View Source [SID1234539862]). The data include the first evidence of anti-tumor activity reported in patients with colorectal cancer (CRC) and appendiceal cancer, as well as previously presented non-small cell lung cancer (NSCLC) findings. AMG 510 continues to be well-tolerated with no dose-limiting toxicities. These data are being presented during a poster discussion at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress.

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The study enrolled 76 patients with KRAS G12C-mutant solid tumors. Data being presented at ESMO (Free ESMO Whitepaper) include a subset of 55 evaluable patients as of the July 2019 data cutoff, including CRC, appendiceal cancer and NSCLC patients from the Phase 1 study. Of the 55 patients, 29 had CRC. Twelve patients with CRC received the target dose of 960 mg once daily and 10 remain on treatment. One patient in this dose cohort experienced a partial response and 10 had stable disease for a disease control rate of 92%. Thirteen of the evaluable patients with NSCLC received 960 mg, of which seven (54%) achieved a partial response at one or more timepoints and six (46%) achieved stable disease, for a disease control rate of 100%. Data across dosing cohorts also showed tumor responses in two evaluable patients with appendiceal cancer with one partial response and one experiencing stable disease.

"KRAS is the most frequently mutated oncogene in human tumors. Although KRASG12C has been a formidable target for nearly four decades, we can now report responses in patients with non-small cell lung, colorectal and appendiceal cancers," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "We are encouraged by these early results, particularly since these patients have progressed after receiving a median of four prior therapies, and in some cases as many as 10. The data suggest there are relevant molecular differences between tumor types. We are initiating combination studies to further explore the potential of AMG 510 in lung and colorectal tumors."

Among the 76 patients enrolled across treatment groups, 52 remain on treatment. The majority of treatment-related adverse events (TRAEs) were grade 1 and 2. Only two TRAEs were grade 3 (diarrhea and anemia). There were no grade 4 or higher TRAEs.

"The prognosis for patients with advanced colorectal cancer remains poor," said Marwan G. Fakih, M.D., clinical study investigator and co-director of the Gastrointestinal Cancer Program, City of Hope, Duarte, Calif. "These are heavily pre-treated colorectal cancer patients, with a median progression-free survival of just over two months, so to see patients still on treatment at the target dose after more than three months is very encouraging."

About the Phase 1 Study
The Phase 1, first-in-human, open-label multicenter study enrolled patients with KRAS G12C- mutant solid tumors. Eligible patients were heavily pretreated with at least two or more prior lines of treatment, consistent with their tumor type and stage of disease. The primary endpoint is safety, and key secondary endpoints include pharmacokinetics, objective response rate (assessed every six weeks), duration of response and progression-free survival. Patients were enrolled in four dose cohorts: 180 mg, 360 mg, 720 mg and 960 mg, taken orally once a day.

When evaluating tumor response, a partial response was defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as at least a 30% decrease in the sum of the diameters of target lesions.1 Stable disease was defined as having neither sufficient tumor shrinkage to qualify for a partial response nor sufficient increase to qualify for progressive disease.

About KRAS
The subject of almost four decades of research, the RAS gene family are the most frequently mutated oncogenes in human cancers.2,3 Within this family, KRAS is the most prevalent variant and is particularly common in solid tumors.3 A specific mutation known as KRAS G12C is found in approximately 13% of non-small cell lung cancers, three to five percent of colorectal cancers and one to two percent of numerous other solid tumors.4 Approximately 30,000 patients are diagnosed each year in the United States with KRAS G12C-mutant cancers.5 KRASG12C has been considered "undruggable" due to a lack of traditional small molecule binding pockets on the protein. Amgen is exploring the potential of KRASG12C inhibition across a broad variety of tumor types.

About Amgen Oncology
Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient’s life – not just their cancer journey – so they can take control of their lives.

For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.

At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do.

For more information, follow us on www.twitter.com/amgenoncology.

On September 27, 2019 Cerus Corporation (Nasdaq: CERS) reported that Kevin D. Green, Cerus’ vice president, finance and chief financial officer will present and provide a corporate update at the 2019 Cantor Global Healthcare Conference in New York City on Wednesday, October 2, 2019 at 3:00 p.m. ET (Press release, Cerus, SEP 27, 2019, View Source [SID1234539847]).

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A live webcast of the presentation will be available on the Investor Relations page of the Cerus web site at View Source A replay of the webcast will be available for approximately two weeks following the completion of the event.

On September 27, 2019 Lannett Company, Inc. (NYSE: LCI) ("Lannett" or the "Company") reported the closing of $86.25 million aggregate principal amount of 4.50% convertible senior notes due 2026 (the "Notes") in a private placement to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Lannett, SEP 27, 2019, View Source;300926947.html [SID1234539863]). Lannett granted the initial purchaser of the Notes a 30-day option to purchase up to an additional $11.25 million aggregate principal amount of the Notes, which option the initial purchaser exercised in full.

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"We are pleased to have successfully completed our recent convertible note offering that has strengthened our capital structure by replacing variable interest rate debt that matures in November 2020 with a substantially lower fixed interest rate convertible bond that matures in October 2026," said Tim Crew, chief executive officer of Lannett. "Our cash balances, following the pay down of the Term A Loan, will exceed the outstanding remaining balance of our Term A Loan. Moreover, the convertible debt is excluded in the calculation of our leverage ratio covenants. We continue to evaluate options with regard to further improving our capital structure."

This press release is neither an offer to sell nor a solicitation of an offer to buy the Notes or the shares of the Company’s common stock issuable upon conversion of the Notes, nor will there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

The Notes and the shares of the Company’s common stock issuable upon conversion of the Notes have not been and will not be registered under the Securities Act, or the securities laws of any other jurisdiction, and may not be offered or sold in the United States absent registration or an applicable exemption from registration requirements.

On September 27, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it will today present results from a Phase Ib study evaluating the efficacy and safety of Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) as a treatment for people with unresectable hepatocellular carcinoma (HCC), the most common form of liver cancer, who have not received prior systemic therapy (Press release, Hoffmann-La Roche, SEP 27, 2019, View Source [SID1234539848]).1

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Data from the non-randomised Tecentriq and Avastin cohort (Arm A) showed clinically meaningful and durable responses after a median follow-up of 12.4 months, with a confirmed objective response rate (ORR) of 36% (95% CI 26–46) by central review per RECIST v1.1. The data also showed that 12% of people had a complete response to treatment and a median duration of response (DOR) was not yet reached. Median progression-free survival (PFS), by central review per RECIST v1.1, a secondary efficacy endpoint in the study, was 7.3 months (95% CI 5.4–9.9).2 Safety for the combination of Tecentriq and Avastin appeared to be consistent with the known safety profile of the individual medicines. No new safety signals were identified.

For the randomised portion of the study (Arm F), evaluating the combination approach with Tecentriq and Avastin versus Tecentriq alone, the primary efficacy endpoint of PFS as assessed by central review per RECIST v1.1 was met, with the combination reducing the risk of disease worsening or death by 45% compared with Tecentriq monotherapy. After a median follow-up of 6.6 months, the results demonstrate the superiority of the combination of Tecentriq and Avastin over Tecentriq monotherapy (hazard ratio =0.55, 80% CI 0.40–0.74, p=0.0108). Median PFS in the Tecentriq and Avastin arm was 5.6 months (95% CI 3.6–7.4) compared with 3.4 months (95% CI 1.9–5.2) in the Tecentriq monotherapy arm.2 Additional secondary endpoints of Arm F are being evaluated and at this time the data remain immature. Safety for both cohorts in Arm F appeared to be consistent with the known safety profile of the individual medicines. No new safety signals were identified.

"We are encouraged by these latest results, which show promising progression-free survival and confirmed objective response rates in people with unresectable hepatocellular carcinoma, a disease for which the unmet medical need is particularly great," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "These data strengthen our belief in the combination of Tecentriq and Avastin in this common form of liver cancer and we look forward to the results from our Phase III study, IMbrave150."

The data (Abstract #LBA39) will be presented at 14:15 in the Proffered Paper session (14:00–15:30) in the Madrid Auditorium (Hall 2), at ESMO (Free ESMO Whitepaper) on Friday 27 September.

In July 2018, the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) for Tecentriq in combination with Avastin as an initial (first-line) treatment for advanced or metastatic HCC based on data from this Phase Ib study.

Earlier this year, enrolment was completed for IMbrave150 (NCT03434379), an open-label, multicentre, randomised Phase III study investigating the combination of Tecentriq and Avastin versus sorafenib in people with unresectable HCC who have not received prior systemic therapy. The study is expected to read out later this year.

Roche has an extensive clinical trial development programme for Tecentriq, with studies ongoing or planned, including multiple Phase III studies, across several types of lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the GO30140 study (NCT02715531)
GO30140 is an open-label, multicentre Phase Ib study evaluating the safety and efficacy of Tecentriq (anti-PD-L1 antibody) administered in combination with Avastin and/or other treatments in people with solid tumours, including HCC. In Arms A and F of the study, people with unresectable HCC who had not received prior systemic therapy were eligible for enrolment. All patients in Arm A received Tecentriq and Avastin. Patients in Arm F were randomised 1:1 to receive Tecentriq and Avastin or Tecentriq monotherapy. Patients on the combination received Tecentriq (1200 mg) and Avastin (15 mg/kg) intravenously every 3 weeks, while those in the monotherapy cohort received Tecentriq (1200 mg) intravenously every 3 weeks. In all cohorts, treatment continued until unacceptable toxicity or loss of clinical benefit. Primary endpoints were ORR (Arm A) and PFS (Arm F) by central review per RECIST v1.1, and safety (both arms).

About hepatocellular carcinoma (HCC)
HCC is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide.1 The disease affects over 750,000 people every year,1,3 with the majority of cases in Asia and almost half of all cases in China.3,4 HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B or C) or alcohol consumption, and typically presents at an advanced stage.1 The prognosis for unresectable HCC remains limited, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis.5

About IMbrave150 (NCT03434379)
IMbrave150 is a global Phase III, multicentre, open-label study of 480 people with unresectable HCC who have not received prior systemic therapy. People are randomised 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. Tecentriq is administered intravenously, 1200 mg on day 1 of each 21-day cycle, and Avastin is administered intravenously, 15 mg/kg on day 1 of each 21-day cycle. Sorafenib is administered by mouth, 400 mg twice per day, on days 1–21 of each 21-day cycle. People receive the combination or the control arm treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Co-primary endpoints are overall survival (OS) and PFS by central review per RECIST v1.1. Secondary endpoints include ORR, PFS, time to progression (TTP) and DOR all assessed by the investigator per RECIST v1.1 and HCC mRECIST, as well as ORR, TTP and DOR by central review per RECIST v1.1, along with time to deterioration (TTD) in patient-reported global health status/quality of life (GHS/QoL).

About the Tecentriq and Avastin combination
There is a strong scientific rationale to support the use of Tecentriq and Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer, and in PD-L1-positive metastatic triple-negative breast cancer.

About Avastin
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour’s ability to grow and spread in the body (metastasize).

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.

To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source