On November 5, 2020 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported its consolidated financial results for the third quarter 2020 and reviewed recent business highlights (Press release, Alnylam, NOV 5, 2020, View Source [SID1234570014]).

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"We are extremely pleased with the performance of ONPATTRO and GIVLAARI in the third quarter, reflecting strong commercial execution and improving market conditions following the more challenging COVID-19 pandemic phase experienced in the second quarter. We’re also excited about the recent positive CHMP opinions for OXLUMO and LEQVIO, moving these potentially transformative investigational RNAi therapeutics closer to approval. We believe that this positions Alnylam to potentially exit 2020 with four revenue-generating products bolstering our sustained growth," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "In addition, our robust late-stage pipeline of investigational medicines continued to advance in the quarter. Notably, we achieved positive results from the ILLUMINATE-B study – demonstrating efficacy and safety for our investigational RNAi therapeutic lumasiran in children under the age of six, including infants. We also achieved continued enrollment in our APOLLO-B and HELIOS-B Phase 3 studies of patisiran and vutrisiran, respectively, in development for the treatment of ATTR amyloidosis with cardiomyopathy. With our recent progress, we now expect to exceed our Alnylam 2020 vision and goals of building a multi-product, global biopharma company with a deep clinical pipeline and a robust, organic product engine to drive future sustainable innovation and value creation. Finally, we look forward to highlighting further progress and future plans at our upcoming virtual R&D Day event in December."

Third Quarter 2020 and Recent Significant Corporate Highlights

Commercial Performance

ONPATTRO

Achieved global net product revenue for the third quarter of 2020 of $82.5 million, representing 24% quarterly growth globally and 21% quarterly growth in the U.S. alone.
Attained over 1,150 patients worldwide on commercial ONPATTRO treatment as of September 30, 2020.
Continued progress with market access efforts across the CEMEA region (Canada, Europe, Middle East, and Africa), with a recent launch in Portugal, conclusion of price negotiations in France, and completion of initial access agreement in Canada.
Continued global expansion with achievement of regulatory approval in Israel.
Received the prestigious 2020 Prix Galien USA Award for Best Biotechnology Product.
GIVLAARI

Achieved global net product revenue for the third quarter of 2020 of $16.7 million.
Attained over 150 patients worldwide on commercial GIVLAARI treatment as of September 30, 2020.
Continued strong market access progress in the U.S., with 10 VBAs finalized to date with commercial payers and confirmed access for over 90% of covered U.S. lives.
Continued progress with market access efforts across the CEMEA region, with ongoing launch in Germany, cohort Temporary Authorization for Use (ATU) supply in France, and named patient sales in other countries.
Received an Improvement of Medical Benefit (ASMR) score of II in France, concluding that GIVLAARI offers significant additional therapeutic value. In 2019, only two new commercial medicines received a similar ASMR score.
In addition, obtained a "Considerable Benefit" rating in Germany and secured a strong health technology assessment (HTA) rating in Italy.
Continued global expansion with approval in Canada and submission of a new drug application in Japan.
Received the NORD 2020 Industry Innovation Award.
R&D Highlights

Advanced patisiran (the non-proprietary name for ONPATTRO), in development for the treatment of the cardiomyopathy of both hereditary and wild-type ATTR amyloidosis.
Continued enrollment in the APOLLO-B Phase 3 study in ATTR amyloidosis patients with cardiomyopathy.
Presented additional clinical data with patisiran – including 24-month results from the global open-label extension (OLE) study and results from an open-label study in patients with hATTR amyloidosis post-orthotopic liver transplant – and published findings from an evaluation of patisiran with concomitant or prior use of TTR stabilizers.
Advanced vutrisiran, a subcutaneously administered investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis.
Continued treating patients in the fully enrolled HELIOS-A Phase 3 study of vutrisiran in hATTR amyloidosis patients with polyneuropathy, and remain on track to report topline results in early 2021.
Continued enrollment in the HELIOS-B Phase 3 study in ATTR amyloidosis patients with cardiomyopathy.
Announced potential for a biannual dosing regimen option for vutrisiran, providing support for further product differentiation as a potential best-in-class agent.
Presented new interim data from the Phase 1/2 open-label extension (OLE) study of givosiran (the non-proprietary name for GIVLAARI) in acute hepatic porphyria (AHP).
Advanced lumasiran, an investigational RNAi therapeutic in development for the treatment of primary hyperoxaluria type 1 (PH1).
Received a positive CHMP opinion from EMA recommending approval of lumasiran for the treatment of PH1 in patients of all ages. If approved, lumasiran will be marketed in Europe under the brand name OXLUMO.
Received a positive scientific opinion from the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) through the Early Access to Medicines Scheme (EAMS).
Presented positive complete results from ILLUMINATE-B, a global Phase 3 pediatric study of lumasiran in PH1 patients less than six years of age, including infants, with preserved renal function.
Continued enrollment in the ILLUMINATE-C Phase 3 study of lumasiran for the treatment of advanced PH1 in patients of all ages.
Alnylam’s partner, Novartis, continued advancing inclisiran, potentially the first and only RNAi therapeutic cholesterol-lowering treatment. Inclisiran is undergoing regulatory review in the U.S. and EU.
Received a positive CHMP opinion from EMA recommending approval of inclisiran for the treatment of adults with hypercholesterolemia or mixed dyslipidemia. If approved, inclisiran will be marketed under the brand name LEQVIO.
Alnylam’s partner, Sanofi, continued advancement of the ATLAS Phase 3 program for fitusiran in patients with hemophilia A or B with and without inhibitors.
Advanced early- and mid-stage RNAi therapeutic pipeline programs.
Continued dosing in the Phase 1 study of ALN-AGT in hypertension.
In collaboration with Regeneron, advanced cemdisiran, an investigational RNAi therapeutic for the treatment of complement-mediated diseases.
Continued enrollment in a Phase 2 clinical trial of cemdisiran monotherapy in patients with IgA nephropathy, with topline results expected in 2021.
Alnylam’s partner Vir Biotechnology presented new data on VIR-2218 (ALN-HBV02) at the European Association for the Study of the Liver Digital International Liver Congress.
In addition, Vir initiated a Phase 2 combination trial of VIR-2218 with pegylated interferon-alpha (PEG-IFN-α), with initial clinical data anticipated in 2021.
The Company is announcing today that it has initiated dosing in a Phase 1 study of ALN-HSD, an investigational RNAi therapeutic targeting HSD17B13 in development for the treatment of nonalcoholic steatohepatitis (NASH). ALN-HSD is being advanced in collaboration with Regeneron.
The Company is announcing today that it will delay its planned filing of an IND for ALN-COV in order to obtain additional pre-clinical efficacy data in models of COVID-19 infection.
ALN-COV is part of a multi-target pre-clinical collaboration with Vir Biotechnology.
Continued progress with investigational RNAi therapeutics for CNS and ocular diseases, including advancement of ALN-APP, in development for the treatment of hereditary cerebral amyloid angiopathy (hCAA) and autosomal dominant Alzheimer’s Disease (ADAD), which remains on track for a CTA filing in mid-2021.
Regeneron exercised its co-development/co-commercialization option on the ALN-APP program, which Alnylam will lead.
Additional Business Updates

Barry Greene, former President of Alnylam, transitioned from Alnylam at the end of the third quarter. Yvonne Greenstreet assumed an expanded role as President and Chief Operating Officer on October 1, 2020.
Closed $150 million R&D funding component of the previously announced $2 billion strategic financing collaboration with Blackstone to accelerate the advancement of RNAi therapeutics.
Expanded global reach of commercialization activities with new third-party distribution agreement with taiba Middle East.
Received recognition from Science magazine as a top employer.
Upcoming Events

Alnylam announced today that it intends to present interim results from the Phase 1 trial of ALN-AGT at the American Heart Association Scientific Sessions 2020 on Friday, November 13.
The Company also announced today that it plans to present a review of its R&D and commercial activities at its upcoming R&D Day event being held virtually December 15 and 16.
In addition, in late 2020, Alnylam intends to:

Achieve regulatory approval for lumasiran in the EU and an FDA action for lumasiran in late 2020.
Alnylam’s partner Novartis expects regulatory approval for inclisiran in the EU and an FDA action for inclisiran in late 2020.
Achieve regulatory approval for ONPATTRO in Taiwan.
Alnylam’s partner Regeneron plans to initiate a Phase 1 study of cemdisiran in combination with pozelimab.
Financial Results for the Quarter Ended September 30, 2020

"The third quarter was very strong, with a rebound in ONPATTRO sales growth, particularly in the U.S., and continued impressive early performance with GIVLAARI. While the pandemic headwinds haven’t completely receded, we believe our teams have been very effective in meeting the needs of patients. As a result of this continued strength and our cautious optimism for the fourth quarter, we are again revising our full-year revenue guidance for ONPATTRO, increasing the range from $280-$300 million to $295-$310 million," said Jeff Poulton, Chief Financial Officer of Alnylam. "Beyond the commercial business, we also closed the $150 million R&D funding component of the Blackstone strategic financing collaboration, finalizing the last piece of a broad relationship that we believe secures our path to self-sustainability without the need for future equity offerings. Looking ahead, we believe we are well positioned to continue executing on our current commercial portfolio, with potential for two additional RNAi therapeutics coming to market, and advancing our broad pipeline of investigational programs to drive future growth."

Net product revenues were $99.2 million in the third quarter 2020 representing 115% growth from the third quarter 2019 primarily as a result of the addition of new patients on therapy and expansion into new markets for ONPATTRO, as well as the ongoing U.S. commercial launch and initial European launch of GIVLAARI.
Net Revenues from Collaborations

Net revenues from collaborations were $26.6 million in the third quarter 2020, an increase from $24.0 million in the third quarter 2019, primarily due to an increase in revenue recognized from our Vir collaboration.
Research & Development (R&D) and Selling, General & Administrative (SG&A) Expenses

R&D expenses were relatively flat on a GAAP basis and increased on a non-GAAP basis in the third quarter 2020 compared to the same period in 2019 primarily due to increased expenses associated with clinical and preclinical activities, personnel, and facilities as we continue to support our long-term strategic growth offset by decreased license fees associated with regulatory filings.
SG&A expenses increased in the third quarter 2020 compared to the same period in 2019 on a GAAP and non-GAAP basis primarily due to increased investment in commercial and medical affairs activity to support the ongoing launches of ONPATTRO and GIVLAARI and initial launch preparation activities for lumasiran. SG&A expenses on a GAAP basis also increased due to a change in estimate of contingent liabilities related to our arbitration with Ionis.
Cash and Investments

Cash, cash equivalents and marketable securities were $1.83 billion at the end of the third quarter 2020 compared to $1.54 billion at the end of 2019. The increase was primarily due to $600.0 million in proceeds received in the second quarter of 2020 from the sale of future royalties and issuance of common stock to Blackstone, partially offset by cash used in our operations to support overall growth.
A reconciliation of GAAP to non-GAAP results for the current quarter is included in the tables of this press release.

2020 Updated Financial Guidance

*Excludes $160-$180 million of expenses primarily related to stock-based compensation and a change in estimate of contingent liabilities from projected GAAP R&D and SG&A expenses.

The strategic financing collaboration with Blackstone under which Alnylam will receive up to $2 billion is expected to enable Alnylam’s achievement of a self-sustainable financial profile without need for future equity financings.

Use of Non-GAAP Financial Measures

This press release contains non-GAAP financial measures, including expenses adjusted to exclude certain non-cash expenses and non-recurring gains outside the ordinary course of the Company’s business. These measures are not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies.

The items included in GAAP presentations but excluded for purposes of determining non-GAAP financial measures for the periods presented in the press release are stock-based compensation expenses, unrealized gains on marketable equity securities, costs associated with our strategic financing collaboration, loss on contractual settlement and change in estimate of contingent liabilities. The Company has excluded the impact of stock-based compensation expense, which may fluctuate from period to period based on factors including the variability associated with performance-based grants for stock options and restricted stock units and changes in the Company’s stock price, which impacts the fair value of these awards. The Company has excluded the impact of the unrealized gains on marketable equity securities, costs associated with our strategic financing collaboration, loss on contractual settlement and change in estimate of contingent liabilities because the Company believes these items are non-recurring transactions outside the ordinary course of the Company’s business.

The Company believes the presentation of non-GAAP financial measures provides useful information to management and investors regarding the Company’s financial condition and results of operations. When GAAP financial measures are viewed in conjunction with non-GAAP financial measures, investors are provided with a more meaningful understanding of the Company’s ongoing operating performance and are better able to compare the Company’s performance between periods. In addition, these non-GAAP financial measures are among those indicators the Company uses as a basis for evaluating performance, allocating resources and planning and forecasting future periods. Non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between GAAP and non-GAAP measures is provided later in this press release.

Conference Call Information

Management will provide an update on the Company and discuss third quarter 2020 results as well as expectations for the future via conference call on Thursday, November 5, 2020 at 8:30 am ET. To access the call, please dial 800-239-9838 (domestic) or +1-323-794-2551 (international) five minutes prior to the start time and refer to conference ID 6976021. A replay of the call will be available beginning at 11:30 am ET on the day of the call. To access the replay, please dial 888-203-1112 (domestic) or +1-719-457-0820 (international) and refer to conference ID 6976021.

A live audio webcast of the call will be available on the Investors section of the Company’s website at www.alnylam.com/events. An archived webcast will be available on the Alnylam website approximately two hours after the event.

About ONPATTRO (patisiran)

ONPATTRO is an RNAi therapeutic that was approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. ONPATTRO is also approved in the European Union, Switzerland and Brazil for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and in Japan for the treatment of hATTR amyloidosis with polyneuropathy. ONPATTRO is an intravenously administered RNAi therapeutic targeting transthyretin (TTR). It is designed to target and silence TTR messenger RNA, thereby blocking the production of TTR protein before it is made. ONPATTRO blocks the production of TTR in the liver, reducing its accumulation in the body’s tissues in order to halt or slow down the progression of the polyneuropathy associated with the disease. For more information about ONPATTRO, visit ONPATTRO.com.

ONPATTRO Important Safety Information

Infusion-Related Reactions

Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO (patisiran). In a controlled clinical study, 19% of ONPATTRO-treated patients experienced IRRs, compared to 9% of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.

To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation

ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness).

Adverse Reactions

The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory tract infections (29%) and infusion-related reactions (19%).

For additional information about ONPATTRO, please see the full Prescribing Information.

About GIVLAARI (givosiran)

GIVLAARI is an RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) approved in the United States and Brazil for the treatment of adults with acute hepatic porphyria (AHP). GIVLAARI is also approved in the European Union for the treatment of AHP in adults and adolescents aged 12 years and older. In the pivotal study, givosiran was shown to significantly reduce the rate of porphyria attacks that required hospitalizations, urgent healthcare visits or intravenous hemin administration at home compared to placebo. GIVLAARI is Alnylam’s first commercially available therapeutic based on its Enhanced Stabilization Chemistry ESC-GalNAc conjugate technology to increase potency and durability. GIVLAARI is administered via subcutaneous injection once monthly at a dose based on actual body weight and should be administered by a healthcare professional. GIVLAARI works by specifically reducing elevated levels of aminolevulinic acid synthase 1 (ALAS1) messenger RNA (mRNA), leading to reduction of toxins associated with attacks and other disease manifestations of AHP. For more information about GIVLAARI, visit GIVLAARI.com.

GIVLAARI Important Safety Information

Contraindications

GIVLAARI is contraindicated in patients with known severe hypersensitivity to givosiran. Reactions have included anaphylaxis.

Anaphylactic Reaction

Anaphylaxis has occurred with GIVLAARI treatment (<1% of patients in clinical trials). Ensure that medical support is available to appropriately manage anaphylactic reactions when administering GIVLAARI. Monitor for signs and symptoms of anaphylaxis. If anaphylaxis occurs, immediately discontinue administration of GIVLAARI and institute appropriate medical treatment.

Hepatic Toxicity

Transaminase elevations (ALT) of at least 3 times the upper limit of normal (ULN) were observed in 15% of patients receiving GIVLAARI in the placebo-controlled trial. Transaminase elevations primarily occurred between 3 to 5 months following initiation of treatment.

Measure liver function tests prior to initiating treatment with GIVLAARI, repeat every month during the first 6 months of treatment, and as clinically indicated thereafter. Interrupt or discontinue treatment with GIVLAARI for severe or clinically significant transaminase elevations. In patients who have dose interruption and subsequent improvement, reduce the dose to 1.25 mg/kg once monthly. The dose may be increased to the recommended dose of 2.5 mg/kg once monthly if there is no recurrence of severe or clinically significant transaminase elevations at the 1.25 mg/kg dose.

Renal Toxicity

Increases in serum creatinine levels and decreases in estimated glomerular filtration rate (eGFR) have been reported during treatment with GIVLAARI. In the placebo-controlled study, 15% of patients receiving GIVLAARI experienced a renally-related adverse reaction. The median increase in creatinine at Month 3 was 0.07 mg/dL. Monitor renal function during treatment with GIVLAARI as clinically indicated.

Injection Site Reactions

Injection site reactions were reported in 25% of patients receiving GIVLAARI in the placebo-controlled trial. Symptoms included erythema, pain, pruritus, rash, discoloration, or swelling around the injection site. One (2%) patient experienced a single, transient, recall reaction of erythema at a prior injection site with a subsequent dose administration.

Drug Interactions

Concomitant use of GIVLAARI increases the concentration of CYP1A2 or CYP2D6 substrates, which may increase adverse reactions of these substrates. Avoid concomitant use of GIVLAARI with CYP1A2 or CYP2D6 substrates for which minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP1A2 or CYP2D6 substrate dosage in accordance with approved product labeling.

Adverse Reactions

The most common adverse reactions that occurred in patients receiving GIVLAARI were nausea (27%) and injection site reactions (25%).

For additional information about GIVLAARI, please see full Prescribing Information.

About LNP Technology

Alnylam has licenses to Arbutus Biopharma LNP intellectual property for use in RNAi therapeutic products using LNP technology.

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

On November 5, 2020 Clovis Oncology, Inc. (NASDAQ:CLVS) reported financial results for the quarter ended September 30, 2020, and provided an update on the Company’s clinical development programs and regulatory and commercial outlook for the rest of the year (Press release, Clovis Oncology, NOV 5, 2020, View Source [SID1234570013]).

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"We are pleased that third quarter revenues for Rubraca grew slightly over the same period in 2019, despite a very challenging sales environment caused by COVID-19, which has severely limited oncology patient visits and cancer diagnoses. In addition, oncology practices have substantially limited traditional in-person sales calls – a trend that we see accelerating – and physicians increasingly prefer digital communications and virtual peer-to-peer interactions. In response to this evolving U.S. oncology market, we are shifting to a hybrid commercial strategy to support these preferences. This new strategy incorporates more targeted in-person promotion, online resources for prescribers customized to their practices and new approaches to peer-to-peer interactions. We believe this hybrid strategy will increase awareness and interest in Rubraca. We have undertaken this change with the goal of returning to growth as rapidly as we can, despite cancer diagnoses and cancer patient visits currently remaining lower than pre-COVID-19," said Patrick J. Mahaffy, President and CEO of Clovis Oncology.

"We also remain focused on our growing pipeline activities and in 2021, we anticipate multiple meaningful clinical, development and regulatory milestones. For Rubraca, we anticipate data from the ATHENA monotherapy arm, and pending data, a potential sNDA filing for the LODESTAR pan-tumor study in the second half of 2021. Interim updates from the LIO-1 study of lucitanib and Opdivo in combination are anticipated in 2021. Following allowance of the IND filings for our peptide-targeted radiotherapeutic candidate, FAP-2286, planned for submission this quarter, we plan to initiate a robust clinical development program in early 2021," Mr. Mahaffy continued.

Third Quarter 2020 Financial Results

Clovis reported net product revenue for Rubraca of $38.8 million for the third quarter of 2020, which included U.S. product revenue of $33.9 million and ex-U.S. product revenue of $4.9 million, compared to net product revenue for Q3 2019 of $37.6 million, which included U.S. net product revenue of $36.5 million and ex-U.S. net product revenue of $1.1 million.

Clovis reported net product revenue for Rubraca of $121.2 million for the nine months ended September 30, 2020, which included U.S. product revenue of $109.8 million and ex-U.S. product revenue of $11.4 million, compared to net product revenue for same period in 2019 of $103.7 million, which included U.S. net product revenue of $101.1 million and ex-U.S. net product revenue of $2.6 million.

Clovis Oncology expects global net product revenue for the fourth quarter 2020 to be in a range of $38 million to $40 million. The effects of COVID-19 on future sales are difficult to predict, especially with the increase in COVID-19 cases in the U.S. and Europe.

Research and development expenses totaled $62.9 million for Q3 2020 and $201.0 million for the first nine months of 2020, compared to $77.9 million and $210.7 million for the comparable periods in 2019. Research and development expenses decreased for the third quarter and the first nine months of 2020 compared to the same periods in the prior year due primarily to lower spending on Rubraca clinical trials. We expect research and development expenses to be lower in the full year 2021 compared to full year 2020.

Selling, general and administrative expenses totaled $38.6 million for Q3 2020 and $123.1 million for the first nine months of 2020, compared to $41.8 million and $137.6 million for the comparable periods in 2019. Selling, general and administrative expenses decreased during the third quarter and first nine months of 2020 compared to the same period in the prior year with savings due to the COVID-19 situation globally and overall cost reduction efforts.

Clovis reported a net loss for the third quarter of 2020 of $78.7 million, or ($0.89) per share, and a net loss of $270.3 million, or ($3.37) per share, for the first nine months of 2020. Net loss for Q3 2019 was $94.1 million, or ($1.72) per share, and $300.9 million, or a net loss of ($5.62) per share, for the first nine months of 2019. Net loss for Q3 and the first nine months of 2020 included share-based compensation expense of $12.5 million and $38.8 million, compared to $14.0 million and $41.7 million for the comparable periods of 2019.

Clovis had $224.7 million in cash and cash equivalents as of September 30, 2020.

As of September 30, 2020, the Company had drawn approximately $85 million under the TPG ATHENA clinical trial financing and had up to $90 million available to draw under the agreement to fund the expenses of the ATHENA trial through Q3 2022.

Based on the Company’s anticipated revenues, spending, available financing sources and existing cash and cash equivalents, the Company believes it has sufficient cash and cash equivalents to fund its operating plan into early 2022, after taking into account any cash repayment (unless refinanced earlier) of the remaining $64.42 million aggregate principal amount of the 2.50% convertible notes, at their maturity in September 2021. Assuming the completion of the offering of $50 million of convertible notes announced today, the additional cash proceeds are anticipated to fund the Company’s operating plan into early 2023.

Net cash used in operating activities was $54.3 million for the third quarter of 2020, down from $57.0 million reported in the third quarter of 2019. Similarly, net cash used in operating activities for the first nine months of 2020 was $196.7 million, compared with $253.5 million for the first nine months of 2019.

Cash burn in Q3 2020 was $37.7 million, which represents a 25 percent sequential decrease from the Q2 2020 cash burn of $50.1 million. Borrowings under the TPG ATHENA financing provided $16.6 million in cash in Q3 2020. Cash burn in the first nine months of 2020 was $154.7 million.

Restructured U.S. Commercial Organization

The COVID-19 pandemic has accelerated a preference by oncology practices for more digital programming, including digital peer-to-peer interactions and reduced in-person promotion. In order to meet these changing preferences, the Company is adopting a hybrid commercial strategy combining increased digital promotional activities, greater online resources and more peer-to-peer interactions with reduced and more targeted in-person promotion. Accordingly, new tools and performance indicators based on this hybrid approach are being rolled out during the fourth quarter, and the U.S. commercial organization has been reduced in size by approximately 45 employees. Despite increased investment in digital promotion, we anticipate an effect of adopting this hybrid model will result in annual cost-savings of approximately $10 million. The Company is adopting this strategy in order to better reach customers in the way they want to be reached with the goal of returning to growth, especially as the ongoing impact of COVID-19 is reduced.

FDA-approved Companion Diagnostic to Identify Eligible mCRPC Patients Added to Rubraca U.S. Label

In late August, the U.S. FDA approved the FoundationOne Liquid CDx, Foundation Medicine’s comprehensive liquid biopsy test for all solid tumors with multiple companion diagnostic indications, including for Rubraca. It is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with specific FDA-approved targeted therapies, including Rubraca. In early October, the companion diagnostic for Rubraca in mCRPC was added to the Rubraca U.S. label.

These events follow the U.S. FDA’s May 2020 approval of Rubraca for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated mCRPC who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. The FDA approved this indication under accelerated approval based on objective response rate and duration of response data from the multi-center, single arm TRITON2 clinical trial.

Data from the TRITON2 study of Rubraca for the treatment of mCRPC harboring BRCA1/2 mutations were published online in the Journal of Clinical Oncology during the quarter. These results supported the May approval and provide additional detail for physicians about the study and about Rubraca as a treatment option for eligible men with mCRPC and a deleterious BRCA1/2 mutation.

Initial Presentations for Lucitanib and Rucaparib Combinations and Preclinical Data for FAP-2286 at Medical Meetings

Six e-posters for Clovis’ three portfolio compounds were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 in September. These included the following:

Initial data from the Phase 1b part of the LIO-1 trial of lucitanib combined with Opdivo (nivolumab) in advanced metastatic solid tumors which identified a recommended Phase 2 dose and showed promising signs of antitumor activity; also, a Trials In Progress e-poster describing the Phase 2 study currently enrolling patients.
The first presentation of preclinical data for FAP-2286, a novel peptide-targeted radionuclide therapy (PTRT), showed the compound potently and selectively binds fibroblast activation protein (FAP); in addition, compelling anti-tumor activity was observed in FAP-expressing tumor models.
New data analyses from pivotal Rubraca studies ARIEL3 and TRITON2 further characterized its safety profile in recurrent ovarian cancer and metastatic castration-resistant prostate cancer (mCRPC), respectively.
Encouraging initial data from the SEASTAR study evaluating Rubraca in combination with Trodelvy (sacituzumab govitecan-hziy).
In addition, in an oral plenary session at the International Gynecologic Cancer Society (IGCS) Digital Annual Global Meeting in September, data from an exploratory analysis of the ARIEL3 clinical study evaluating Rubraca as maintenance treatment in recurrent ovarian cancer were presented. The findings demonstrate that rucaparib maintenance treatment can lead to a clinically meaningful delay in starting subsequent therapy and lasting clinical benefits in patients with BRCA1- or BRCA2-mutant ovarian cancer.

The data described here are available online at www.clovisoncology.com/pipeline/scientificpresentations.

Lucitanib Combination Studies Underway

The Phase 2 portion of LIO-1 trial evaluating lucitanib and Opdivo in combination in advanced solid tumors (Phase 1b) and gynecologic cancers (Phase 2) is open for enrollment and the first patient was treated in August. Clovis intends to submit updated interim data from the LIO-1 study for presentation at a 2021 medical meeting.

FAP-2286 and Radionuclide Therapy Development Program

Clovis intends to submit two Investigational New Drug (IND) applications for FAP-2286 for use as imaging and treatment agents respectively. Following allowance of the INDs by the U.S. FDA, Clovis will initiate a Phase 1 study to determine the dose and tolerability of the FAP-targeting therapeutic agent, with expansion cohorts planned in multiple tumor types. The FAP-targeting imaging agent will be utilized to identify tumors that contain FAP for treatment in the Phase 1 study.

Conference Call Details

Clovis will hold a conference call to discuss Q3 2020 results this morning, November 5, at 8:30am ET. The conference call will be simultaneously webcast on the Clovis Oncology web site www.clovisoncology.com, and archived for future review. Dial-in numbers for the conference call are as follows: US participants (877) 698-7048, International participants (647) 689-5448, conference ID: 2999168.

About Rubraca (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed multiple tumor types, including ovarian and prostate cancers, as monotherapy and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway. Clovis holds worldwide rights for Rubraca.

In the United States, Rubraca is approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Rubraca is also approved in the United States for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca. Additionally, Rubraca is approved in the U.S. 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. Select patients for therapy based on a FDA-approved companion diagnostic for Rubraca. 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. The TRITON3 clinical trial is expected to serve as the confirmatory study for the Rubraca accelerated approval in mCRPC.

In Europe, Rubraca is approved for the maintenance treatment of adults with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. Rubraca is also approved in Europe for the treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Rubraca is an unlicensed medical product outside of the U.S. and Europe.

About Lucitanib

Lucitanib is an investigational angiogenesis inhibitor, which inhibits vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDGFRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3). Emerging clinical data support the combination of angiogenesis inhibitors and immunotherapy to increase effectiveness in multiple cancer indications. Angiogenic factors, such as vascular endothelial growth factor (VEGF), are frequently up-regulated in tumors and create an immunosuppressive tumor microenvironment. Use of antiangiogenic drugs may reverse this immunosuppression and augment response to immunotherapy. Clovis holds global rights for lucitanib excluding China.

Lucitanib is an unlicensed medical product.

About FAP-2286

FAP-2286 is a preclinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein alpha (FAP). FAP is highly expressed in many epithelial cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas. Clovis holds U.S. and global rights for FAP-2286 excluding Europe.

FAP-2286 is an unlicensed medical product.

On November 5, 2020 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing XCART, a personalized CAR T platform technology engineered to target patient- and tumor-specific neoantigens, reported that Jeffrey Eisenberg, Chief Executive Officer of Xenetic will present at the H.C. Wainwright 6th Annual Israel Conference on Tuesday, November 12, 2020 at 8:00 AM EST (Press release, Xenetic Biosciences, NOV 5, 2020, View Source [SID1234570012]).

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In addition to the presentation, management will also be available to participate in virtual one-on-one meetings with qualified members of the investor community who are registered to attend the conference.

A live video webcast of the presentation will be available on the IR Calendar page of the Investors section of the Company’s website (xeneticbio.com). The video webcast replay will be made available two hours following the event and will be archived for 90 days.

On November 5, 2020 Selecta Biosciences, Inc. (NASDAQ: SELB), a biotechnology company leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses, reported financial results for the third quarter ended September 30, 2020 and provided corporate updates (Press release, Selecta Biosciences, NOV 5, 2020, View Source [SID1234570011]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"This past quarter has been productive for our team as we have continued to progress our clinical programs," said Carsten Brunn, Ph.D., President and CEO of Selecta. "We reported topline data from the Phase 2 COMPARE trial of SEL-212 which demonstrated the potential of our ImmTOR platform when combined with a highly immunogenic enzyme, and we commenced the Phase 3 DISSOLVE program in partnership with Sobi. We look forward to continuing to build our pipeline with our gene therapy programs in MMA and OTC deficiency, and our second enzyme program in IgA nephropathy. Our strategy is focused on leveraging ImmTOR to amplify the efficacy of biologic therapies and restore self-tolerance in autoimmune diseases."

Recent Highlights and Anticipated Upcoming Milestones:

Two Key Clinical Milestones for SEL-212: In September, Selecta and Sobi commenced the Phase 3 clinical program, known as DISSOLVE, with Selecta running the program and Sobi reimbursing Selecta for costs associated with the program. The DISSOLVE clinical program consists of two double-blind, placebo-controlled trials of SEL-212 (NCT04513366) in which SEL-212 will be evaluated at two doses of ImmTOR (0.1 mg/kg and 0.15 mg/kg), and one dose of pegadricase (0.2 mg/kg) in both studies. Each trial will aim to enroll 105 patients (35 at each dose level and 35 on placebo). In DISSOLVE I, safety and efficacy will be evaluated at six months and will have a six-month extension. DISSOLVE II will assess safety and efficacy at only the six-month time point, with no extension. The primary endpoint in both studies is serum uric acid levels (SUA) less than 6 mg/dL at six months, a well-validated measure of disease severity in chronic refractory gout. Topline data from the DISSOLVE program is expected in the second half of 2022. Also in September, the Company reported topline results from the Phase 2 COMPARE clinical trial in which a once-monthly dose of SEL-212 (ImmTOR + pegadricase) was compared to biweekly doses of pegloticase. Sobi has in-licensed SEL-212 and assumes responsibility for all development (excluding DISSOLVE, which is run by Selecta and funded by Sobi), regulatory, and commercial activities, and expenses in all markets outside China. Selecta is eligible to receive potential development, regulatory, and commercial milestone payments of up to $630 million, and tiered double-digit royalties on net sales.

Granted Rare Pediatric Disease Designation with AskBio for Gene Therapy for Methylmalonic Acidemia: Selecta and AskBio have received Rare Pediatric Disease Designation from the U.S. Food and Drug Administration (FDA) to develop MMA-101 in combination with ImmTOR for the treatment of isolated methylmalonic acidemia (MMA) due to methylmalonyl-CoA mutase (MMUT) gene mutations. Selecta and AskBio expect to commence a Phase 1 clinical trial in this program in the first half of 2021, with preliminary data expected by the end of 2021.

Entered into Research License and Option Agreement with IGAN Biosciences for the Use of ImmTOR in IgA Nephropathy: In October, Selecta and IGAN Biosciences reached an agreement which provides Selecta with the option to an exclusive license for the rights to develop and commercialize the ImmTOR platform in combination with IGAN’s immunoglobulin A (IgA) protease for the treatment of IgA nephropathy (IgAN). Selecta intends to submit its Investigational New Drug Application (IND) for IgA nephropathy by the end of 2021. IgA nephropathy is characterized by deposition of galactose-deficient IgA1 immunoglobulin in the glomerular mesangium and is a leading contributor to development of chronic kidney disease and renal failure. There are no approved therapies for the treatment of IgAN.
Third Quarter 2020 Financial Results:

Cash Position: Selecta had $147.6 million in cash, cash equivalents, and restricted cash as of September 30, 2020, which compares to cash, cash equivalents, and restricted cash of $91.6 million as of December 31, 2019. Selecta believes its available cash, cash equivalents, and restricted cash as of September 30, 2020 will enable Selecta to fund operating expenses and capital expenditure requirements into the first quarter of 2023.

• Net cash provided by operating activities was $42.1 million for the nine months ended September 30, 2020, as compared to $38.6 million used for the same period in 2019.
Revenue: Revenue recognition for the third quarter 2020 was $4.6 million. During the three months ended September 30, 2020, we recognized $4.3 million under the license agreement with Sobi resulting from the shipment of clinical supply and the reimbursement of costs incurred for the Phase 3 DISSOLVE clinical program and $0.3 million for shipments under the collaboration agreement with Sarepta. During the three months ended September 30, 2019, Selecta did not recognize revenue.
Research and Development Expenses: Research and development expenses for the third quarter 2020 were $14.0 million, which compares with $8.1 million for the same period in 2019. The increase in cost was primarily the result of the initiation of the Phase 3 DISSOLVE clinical program. These costs are subject to the cost reimbursement arrangement under the license with Sobi. The increase in expense was also the result of the completion of its Phase 2 COMPARE trial for SEL-212 and for the AskBio Collaboration.

General and Administrative Expenses: General and administrative expenses for the third quarter 2020 were $4.4 million, which compares with $3.7 million for the same period in 2019. The increase in costs was the result of expenses incurred for facilities, legal and professional fees offset by decreased travel expense.

Net Loss: For the third quarter 2020, Selecta reported a net loss of $9.7 million, or $0.09 per share, compared to a net loss of $12.0 million, or $0.26 per share, for the same period in 2019.
Conference Call and Webcast Reminder:

Selecta management will host a conference call at 8:30 a.m. ET today to provide a corporate update and review the company’s third quarter 2020 financial results. Individuals may participate in the live call via telephone by dialing (844) 845-4170 (domestic) or (412) 717-9621 (international) and may access a teleconference replay for one week by dialing (877) 344-7529 (domestic) or (412) 317-0088 (international) and using confirmation code 10138608. Investors and the public can access the live and archived webcast of this call via the Investors & Media section of the company’s website, www.selectabio.com.

On November 5, 2020 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that on November 4, 2020 it entered into a privately negotiated exchange and purchase agreement (the "Agreement") with a holder of its currently outstanding 4.50% Convertible Senior Notes due 2024 (the "Existing 2024 Notes") (Press release, Clovis Oncology, NOV 5, 2020, View Source [SID1234570010]). Pursuant to the Agreement, in exchange for $64,842,000 aggregate principal amount of Existing 2024 Notes held by the holder (which is currently convertible into approximately 8.9 million shares of common stock), Clovis Oncology has agreed to issue to the holder a number of shares of the Company’s common stock (the "Exchanged Shares") utilizing an exchange ratio that is based in part on the daily volume-weighted average prices ("VWAPs") per share of Clovis Oncology’s common stock during a seven-trading day pricing period following execution of the Agreement.

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In addition, pursuant to the Agreement, Clovis Oncology has also agreed to sell to the holder $50,000,000 aggregate principal amount of a new series of 4.50% Convertible Senior Notes due 2024 (the "New 2024 Notes") at a purchase price of $1,000 per $1,000 principal amount thereof. Also, Clovis Oncology has granted the holder a 13-day option to purchase up to an additional $20,000,000 aggregate principal amount of New 2024 Notes on the same terms and conditions.

About the Debt Exchange

The number of Exchanged Shares to be issued by Clovis Oncology to the holder will be calculated utilizing an exchange ratio that is based in part on the average VWAPs of Clovis Oncology’s common stock (subject to a floor) during a seven-trading day pricing period beginning on November 5, 2020 and ending on, and including, November 13, 2020. Assuming such average VWAP is $5.67 per share, which is the last reported sale price of Clovis Oncology’s common stock on the Nasdaq Global Select Market on November 4, 2020, 13,038,683 Exchanged Shares would be issuable pursuant to the debt exchange transaction. However, in the event that Clovis Oncology’s stock price declines during the pricing period, Clovis Oncology will be required to issue more shares, but in no event more than 15,696,240 Exchanged Shares are issuable pursuant to the debt exchange transaction.

About the New 2024 Notes

The New 2024 Notes will bear interest at a rate of 4.50% per annum, payable semi-annually in arrears on February 1st and August 1st of each year. The New 2024 Notes will mature on August 1, 2024 unless earlier converted or repurchased. The holders of the New 2024 Notes may convert their notes at their option at any time prior to the close of business on the business day immediately preceding the maturity date at an initial conversion rate of 160.3334 shares of Clovis Oncology’s common stock per $1,000 principal amount of notes, which is equivalent to an initial conversion price of approximately $6.24 per share of common stock. The initial conversion price of the notes represents a premium of approximately 10% to the last reported sale price, $5.67 per share, of Clovis Oncology’s common stock on November 4, 2020.

Clovis Oncology will not have the right to redeem the New 2024 Notes prior to their maturity. Holders of the New 2024 Notes may require Clovis Oncology to repurchase for cash all or part of their notes upon certain fundamental changes at a repurchase price equal to 100% of the principal amount of the New 2024 Notes to be repurchased, plus accrued and unpaid interest to, but excluding, the fundamental change repurchase date. In addition, following certain corporate events that occur prior to the maturity date, Clovis Oncology will, in certain circumstances, increase the conversion rate for a holder who elects to convert its New 2024 Notes in connection with such corporate event.

The above summary of the terms of the New 2024 Notes is qualified in its entirety by and should be read with the Indenture governing the New 2024 Notes, the form of which is anticipated to be filed with the Securities and Exchange Commission on or about November 5, 2020.

Clovis Oncology intends to use the net proceeds from the sale of the New 2024 Notes for general corporate purposes, including repayment, repurchase or refinance of its debt obligations, sales and marketing expenses associated with Rubraca (rucaparib), funding of its development programs, payment of milestones pursuant to its license agreements, general and administrative expenses, acquisition or licensing of additional product candidates or businesses and working capital.

The issuance of the Exchanged Shares, the New 2024 Notes in the transaction and any shares of common stock issuable upon conversion of such New 2024 Notes have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state securities law, and, unless so registered, the New 2024 Notes and any such shares may not be offered or sold in the United States except pursuant to an applicable exemption from the registration requirements of the Securities Act and applicable state securities laws. Clovis Oncology has agreed to file a registration statement for the resale of the shares of common stock issuable upon the conversion of the New 2024 Notes purchased by the holder. This press release does not constitute an offer to sell, or a solicitation of an offer to buy, any security and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offering would be unlawful.

About the Settlement of the Transactions

The exchange and purchase transaction will settle in two parts. Approximately 8.9 million of the Exchanged Shares are expected to be issued on or about November 6, 2020 and the remainder will be issued within two business days following the seven-trading day pricing period and the final calculation of the exchange ratio, which is expected to occur on or about November 17, 2020. The sale of the New 2024 Notes is expected to occur on or about November 17, 2020. In each case, the settlement of the exchange and purchase transaction is subject to the satisfaction of customary closing conditions.

J.P. Morgan and BofA Securities acted as structuring banks to Clovis Oncology in connection with the transactions.