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Madrigal Pharmaceuticals Reports 2018 Third Quarter Financial Results and Highlights Upcoming Clinical Events

On November 6, 2018 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) reported its third quarter 2018 financial results and described upcoming clinical events (Press release, Synta Pharmaceuticals, NOV 6, 2018, View Source [SID1234530859]):

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"Madrigal made important progress thus far in 2018 to advance the development of MGL-3196, through successful completion of Phase 2 studies in NASH and dyslipidemia. We expect to begin a Phase 3 study in NASH in late 2018 or early 2019, subject to regulatory approval. We are evaluating the trial design and objectives of a Phase 3 study in dyslipidemia which could begin in 2019," stated Paul Friedman, M.D., Chief Executive Officer of Madrigal. "We are adding appropriate personnel resources as necessary to handle these development activities, and we believe we have significant financial resources to fund our currently planned Phase 3 programs.

Becky Taub, M.D., CMO and Executive VP, Research & Development of Madrigal added, "We are looking forward to presenting our Phase 2 NASH clinical data in a presidential plenary session on November 12, 2018, at The Liver Meeting 2018 at AASLD. We continue to believe in the potential of MGL-3196 to resolve NASH and improve multiple atherogenic lipids, and we are eager to move ahead with our Phase 3 clinical programs.

Financial Results for the Three Months and Nine Months Ended September 30, 2018

As of September 30, 2018, Madrigal had cash, cash equivalents and marketable securities of $488.5 million, compared to $191.5 million at December 31, 2017. The increase in cash and marketable securities resulted primarily from the net proceeds of $311.8 million from Madrigal’s public offering of common stock in June 2018, partially offset by cash used in operations of $19.2 million.

Operating expenses were $11.3 million and $26.2 million, respectively, for the three month and nine month periods ended September 30, 2018, compared to $8.6 million and $23.2 million in the comparable prior year periods.

Research and development expenses for the three month and nine month periods ended September 30, 2018 were $6.2 million and $16.5 million, respectively, compared to $6.7 million and $17.9 million in the comparable prior year periods. The decreases are primarily attributable to completion of treatment in our Phase 2 clinical studies in 2018.

General and administrative expenses for the three month and nine month periods ended September 30, 2018 were $5.1 million and $9.7 million, respectively, compared to $2.0 million and $5.3 million in the comparable prior year periods. The increases are due primarily to higher non-cash stock compensation expense from stock option awards.

Interest income for the three month and nine month periods ended September 30, 2018 was $2.8 million and $4.7 million, respectively, as compared to $174 thousand and $342 thousand in the comparable prior year periods. The change in interest income was due primarily to a higher average principal balance in our investment account in 2018, and increased interest rates.

Clinical Program Summaries for MGL-3196

NASH

Non-alcoholic Steatohepatitis (NASH) is a common liver disease in the United States and worldwide, unrelated to alcohol use, that is characterized by a build-up of fat in the liver, inflammation, damage (ballooning) of hepatocytes and increasing fibrosis. Although people with NASH may feel well and often do not know they have the disease, NASH can lead to permanent damage, including cirrhosis and impaired liver function in a high percentage of patients.

In October 2016, the first patient was treated in the ongoing Phase 2 trial of MGL-3196 for the treatment of NASH. The randomized, double-blind, placebo-controlled, multi-center Phase 2 study enrolled 125 patients 18 years of age and older with liver biopsy-confirmed NASH and included approximately 25 clinical sites in the United States. Patients were randomized to receive either MGL-3196 or placebo in a 2:1 ratio.

The primary endpoint of the study was the reduction of liver fat at 12 weeks compared with baseline (relative change), assessed by MRI-PDFF. Key secondary endpoints at 36 weeks included: reduction in liver fat compared with baseline (relative change), also assessed by MRI-PDFF; a two-point reduction in NAS (NALFD activity score) on biopsy; resolution of NASH on biopsy; and, safety and tolerability based on adverse events and changes in laboratory values.

The primary endpoint of the study at 12 weeks was achieved. Liver fat was reduced by 36.3% in all MGL-3196 treated patients (78) and 42.0% in a pre-specified group of high exposure MGL-3196 treated patients (44/78), as compared with 9.6% median reduction in liver fat in 38 placebo treated patients. These results were statistically significant (p<0.0001) for both MGL-3196 treatment groups. Further, 75% of the high-exposure MGL-3196 treated patients showed liver fat reductions of >30%.

At 36 weeks, MGL-3196 achieved multiple key secondary endpoints including a sustained highly significant (p<0.001) reduction in liver fat compared to placebo as

measured by MRI-PDFF; mean relative fat reduction for MGL-3196 was 37% versus 8.9% for placebo. MGL-3196 was associated with a greater percentage of subjects with a 2-point improvement in NAS (56% of 73 patients vs 32% of 34 placebo subjects, p=0.02). NASH resolution (NR) was seen in 27% of MGL-3196 compared with 6% of placebo subjects, p=0.02. MGL-3196 patients with > 30% fat reduction on Week 12 MRI-PDFF demonstrated a higher percentage of 2-point improvement in NAS (70%, p=0.001) and NR (39%, p=0.001) compared with placebo, demonstrating a strong relationship between early reduction in liver fat as demonstrated by week 12 MRI-PDFF and NASH improvement on liver biopsy at Week 36. In patients with NASH Resolution, 35% of the MGL-3196 treated patients and no placebo patients had more advanced NASH (baseline NAS >5).

At Week 36, MGL-3196 treated patients showed sustained reduction of fibrosis biomarkers. In MGL-3196 patients with NASH resolution, fibrosis also resolved in 50% of patients and was decreased statistically significantly relative to all placebo patients.

There were statistically significant reductions in liver enzymes in MGL-3196 treated patients compared to placebo treated patients; reductions of greater magnitude were achieved with longer duration of MGL-3196 treatment. Statistically significantly more MGL-3196 treated patients than placebo treated patients had normalization of ALT (alanine transaminase).

Similar to week 12, at week 36 there were sustained, statistically significant reductions in low-density lipoprotein cholesterol (LDL-C), triglycerides, ApoB and lipoprotein(a).

MGL-3196 was well tolerated in this trial with mostly mild and a few moderate AEs which were balanced between drug treated and placebo patients. There was an increase in incidence of mild transient diarrhea in MGL-3196-treated, often a single episode, at the start of treatment. Diarrhea incidence was not increased later in the study.

Based on liver enzyme inclusion criteria, some patients are receiving extended treatment beyond 36 weeks for up to 36 additional weeks. All patients in this extension study will receive MGL-3196 and only non-invasive assessments will be made, including serial MRI-PDFF, safety labs, and circulating biomarkers.

Additional information about the study [NCT02912260] can be obtained at www.ClinicalTrials.gov.

HeFH

Heterozygous familial hypercholesterolemia (HeFH), and a much rarer form called homozygous familial hypercholesterolemia (HoFH), are severe genetic dyslipidemias typically caused by inactivating mutations in the LDL receptor. Both forms of FH lead to early onset cardiovascular disease. HeFH, the most common dominantly inherited disease, is present in up to 1 in 200 people; the disease is found in higher frequencies

in certain more genetically homogenous populations. Treatments exist for both HeFH and HoFH but many patients (as many as 40 percent of HeFH patients) are not able to reach their cholesterol (LDL-C) reduction goals on these therapies, reflecting the lifetime burden of cholesterol buildup in their bodies. Based on evidence of impressive LDL cholesterol lowering in Phase 1, and data suggesting that MGL-3196 has a mechanism of action that is different from and complementary to statins, Madrigal initiated a Phase 2 proof-of-concept trial in HeFH in February 2017 and enrolled 116 patients.

In this Phase 2 HeFH trial, patients who were not at their LDL-C goal were randomized in a 2:1 ratio to receive either MGL-3196 or placebo, in addition to their current cholesterol lowering regimen, which included approximately 75% taking high intensity statins (20/40 mg rosuvastatin or 80 mg atorvastatin), and about 2/3 of patients also taking ezetimibe. MGL-3196 treated patients (placebo corrected) achieved highly significant (p< 0.0001) LDL-C lowering of 18.8%, and 21% LDL-C lowering in those on an optimal dose of MGL-3196. LDL-C lowering was 28.5% in MGL-3196 treated compared to placebo in a prespecified group of patients who did not tolerate high intensity statin doses. Highly significant reductions (p<0.0001) relative to placebo were also observed with ApoB, triglycerides (TG) (25-31%), apolipoprotein CIII (Apo CIII) and Lp(a) (25-40%) in all MGL-3196 treated patients and prespecified subgroups, irrespective of statin treatment.

MGL-3196 was well-tolerated with primarily mild and some moderate AEs, the numbers of which were balanced between placebo and drug-treatment groups.

About MGL-3196

Among its many functions in the human body, thyroid hormone, through activation of its beta receptor, plays a central role in controlling lipid metabolism, impacting a range of health parameters from levels of serum cholesterol and triglycerides to the pathological buildup of fat in the liver. Attempts to exploit this pathway for therapeutic purposes in cardio-metabolic and liver diseases have been hampered by the lack of selectivity of older compounds for the thyroid hormone receptor (THR)-β, chemically-related toxicities and undesirable distribution in the body.

Madrigal recognized that greater selectivity for thyroid hormone receptor (THR)-β and liver targeting might overcome these challenges and deliver the full therapeutic potential of THR-β agonism. Madrigal believes that MGL-3196 is the first orally administered, small-molecule, liver- directed, truly β-selective THR agonist. MGL- 3196 has now demonstrated in two Phase 2 double-blind, placebo-controlled trials in NASH and HeFH the potential for a broad array of therapeutically beneficial effects, improving components of both metabolic syndrome, such as insulin resistance and dyslipidemia, and fatty liver disease, including lipotoxicity and inflammation. Based on evidence of these pleiotropic actions, coupled with an excellent safety profile, Madrigal plans to initiate a Phase 3 clinical program in NASH.

EyePoint Pharmaceuticals Reports Fiscal First Quarter 2019 Financial Results and
Highlights Recent Clinical and Operational Developments

On November 6, 2018 EyePoint Pharmaceuticals, Inc. (NASDAQ: EYPT), a specialty biopharmaceutical company committed to developing and commercializing innovative ophthalmic products, reported operating and financial results for its fiscal 2019 first quarter ended September 30, 2018 and highlighted recent clinical and operational developments (Press release, pSivida, NOV 6, 2018, View Source [SID1234530856]).

"The approval of YUTIQ by the U.S. FDA in October marked a significant achievement for EyePoint and validates the Company’s innovation and ability to develop an effective treatment to decrease recurrence of uveitic flares from non-infectious posterior segment uveitis that can result in blindness," said Nancy Lurker, President and Chief Executive Officer of EyePoint Pharmaceuticals. "Following the positive reception by retina and uveitis specialists of the clinical data presented for YUTIQ at the American Academy of Ophthalmology 2018 Annual Meeting, we believe that we are well-positioned for a successful product launch planned in the first quarter of calendar 2019. In addition, we are scaling up our manufacturing of DEXYCU ahead of an anticipated launch in the first half of calendar 2019."

Recent Clinical & Operational Highlights

In October 2018, the U.S. Food and Drug Administration (FDA) approved YUTIQ (fluocinolone acetonide intravitreal implant) 0.18 mg, a three-year micro-insert for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye. YUTIQ utilizes the Company’s Durasert drug delivery technology and is an intravitreal micro-insert designed to deliver drug consistently over 36 months. The approval occurred 24 days in advance of the PDUFA date of November 5th.

At the American Academy of Ophthalmology (AAO) 2018 Annual Meeting in Chicago, IL, 24-month efficacy and safety data supporting YUTIQ was presented during the Retina Subspecialty day at a breakthrough presentation entitled, "24-month Evaluation of Fluocinolone Acetonide Intravitreal Insert Treatment for Non-Infectious Posterior Uveitis". These data demonstrated that the recurrence rate in randomized eyes treated with YUTIQ was significantly lower than in sham eyes (59.8% vs. 97.6%, respectively; p<0.001) at 24-months of the three-year trial. Safety and side effects were consistent with those reported for previous analyses of earlier timepoints.

In August, safety and efficacy data from the Phase 3 clinical trial of DEXYCU compared to prednisolone acetate 1.0% ophthalmic drops for the treatment of inflammation post-cataract surgery were published in the Journal of Cataract & Refractive Surgery. Results demonstrated similar efficacy and safety between both products in treating inflammation post cataract surgery with a preference of DEXYCU compared to drops.

EyePoint granted Ocumension Therapeutics, a China-based ophthalmology company, an exclusive license to develop and commercialize EyePoint’s three-year micro insert product using the Durasert technology for chronic, non-infectious uveitis affecting the posterior segment of the eye in the greater China territory, which is comprised of China, Hong Kong, Macau and Taiwan. EyePoint will receive a one-time upfront payment of $1.75 million and is eligible to receive up to an additional $10.0 million if certain future prespecified development, regulatory and commercial sales milestones are achieved by Ocumension. Ocumension will be responsible for funding the clinical development of EyePoint’s three-year micro-insert product using the Durasert technology for chronic, non-infectious posterior segment uveitis in Greater China. EyePoint will supply product for the clinical trials.

John Landis, Ph.D., M.S., was appointed to the EyePoint Board of Directors in October 2018. Dr. Landis brings more than 30 years of pharmaceutical research and development experience from senior level roles held at Schering-Plough Corporation, Pharmacia Corporation and The Upjohn Company.

EyePoint’s Board of Directors approved a change of the Company’s fiscal year-end to December 31 from the current fiscal year-end of June 30. The Company believes this change will align its financial reporting periods to that of its peer group in the industry and better facilitate assessment of the Company’s financial performance. The Company will file transitional audited financial statements on Form 10-KT for the six-month period ending December 31, 2018.

Fiscal First Quarter 2019 Results

Revenue for the three months ended September 30, 2018 totaled $486,000 compared to $385,000 for the prior year quarter. Revenues in both periods were primarily derived from royalty income under existing collaboration agreements.

Operating expenses for the quarter ended September 30, 2018 increased to $14.0 million from $6.4 million a year earlier, due primarily to initial investments in sales and marketing infrastructure and program costs, amortization of the DEXYCU intangible asset, professional services and stock-based compensation. Non-operating expense, net in the quarter ended September 30, 2018 totaled $19.6 million and consisted primarily of a non-cash change in fair value of derivative liability and interest expense on our term loan. Net loss for the quarter ended September 30, 2018 was $33.1 million, or $0.44 per share, compared to a net loss of $6.0 million, or $0.15 per share, for the prior year quarter.

Cash and cash equivalents at September 30, 2018 totaled $55.8 million compared to $38.8 million at June 30, 2018. The cash balance of September 30, 2018 reflects proceeds of $28.9 million from the exercise of warrants in the quarter.

Conference Call Information

EyePoint will host a conference call today, Tuesday, November 6, 2018, at 8:00 AM ET, to discuss the fiscal first quarter 2019 financial results and recent clinical and operational developments. To access the conference call, please dial (877) 312-7507 (local) or (631) 813-4828 (international) at least 10 minutes prior to the start time and refer to conference ID 3098959. A live webcast will be available on the Investor Relations section of the corporate website at View Source A replay of the webcast will also be available on the corporate website.

Ionis Reports Third Quarter 2018 Financial Results

On November 6, 2018 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today reported financial results for the third quarter of 2018 and highlighted its recent business and pipeline successes.

"We enter the fourth quarter in a position of financial strength, driven by strong worldwide SPINRAZA sales. In addition, we achieved numerous successes during the quarter that advanced our pipeline, technology and business and contributed to our financial strength. In 2019 and beyond, we are positioned for continued growth bolstered by the addition of TEGSEDI commercial revenue," said Stanley T. Crooke, M.D., Ph.D., chairman of the board and chief executive officer of Ionis. "Beyond our commercial-stage drugs, we have a broad and growing pipeline of innovative programs we are advancing toward the market. We continue to advance our antisense technology, expanding its application to more diseases, both rare and common. An example of this is our LICA technology, which was further validated by the results from the Phase 2 study of AKCEA-APO(a)-LRx – our largest and longest study to date with a LICA drug – which demonstrated significant reductions in Lp(a) and an attractive safety profile. We also continue to expand our Ionis-owned pipeline and our existing relationships with partners. The successes we are achieving with our commercial-stage drugs and in advancing our pipeline have increased our financial strength and our ability to deliver innovative new drugs to patients in need."

Third Quarter 2018 Financial Highlights

·
Revenues increased year-to-date by more than 15 percent compared to 2017

o
Total revenue was $145 million and $408 million for the third quarter and year-to-date 2018, respectively, compared to $118 million and $346 million for the same periods in 2017

o
Commercial revenue from SPINRAZA for year-to-date 2018 was $168 million, a nearly three-fold increase over year-to-date 2017

o
Commercial revenue was 45 percent of Ionis’ total revenue in the first nine months of 2018 compared to less than 20 percent for the same period in 2017, reflecting Ionis’ transition to a commercial-stage company

·
On track for third consecutive year of pro forma operating profitability while investing in the launches of two drugs

o
GAAP operating results were a loss of $19 million and $72 million for the third quarter and year-to-date 2018, respectively, compared to operating income of $11 million and $37 million for the same periods in 2017

o
Pro forma operating income was $16 million and $25 million for the third quarter and year-to-date 2018, respectively, compared to $33 million and $101 million for the same periods in 2017

o
Operating expenses increased primarily due to higher SG&A expenses related to preparing to launch TEGSEDI and WAYLIVRA

·
Substantial cash position of $2 billion enabling investment in commercial products and pipeline

o
The increase in Ionis’ cash position was primarily due to the $1 billion Ionis received from Biogen for the 2018 strategic neurology collaboration

"Our strong third quarter financial results put us on track for our third consecutive year of pro forma operating income. In the fourth quarter, we are excited to add TEGSEDI commercial sales to our growing SPINRAZA revenue and substantial base of R&D revenue, positioning us for significant revenue growth going forward," said Elizabeth L. Hougen, chief financial officer of Ionis. "Importantly, we are in a strong financial position with sustainable profitability and $2 billion in cash even as we support the launch of TEGSEDI in multiple markets and prepare for the launch of WAYLIVRA. Further, our financial strength coupled with our business strategy provides us with the flexibility to maximize the value of our robust antisense technology platform and innovative pipeline of drugs."

All pro forma amounts referred to in this press release exclude non-cash compensation expense related to equity awards. Please refer to the reconciliation of pro forma and GAAP measures, which is provided later in this release. Additionally, Ionis has labeled its prior period financial statements "as revised" to reflect the new revenue recognition accounting standard the Company adopted on January 1, 2018.

Business Highlights

·
SPINRAZA – the first and only approved treatment for people with spinal muscular atrophy

o
SPINRAZA sales continued to grow in the third quarter, both in the U.S. and ex-U.S., with global sales of more than $1 billion for year-to-date 2018, as reported by Biogen.

o
Nearly 6,000 SMA patients were on SPINRAZA as of the third quarter.

o
In the U.S., the number of adult patients on therapy grew by over 20 percent compared to the second quarter. Adult SMA patients, which represent the largest and most undertreated patient segment, accounted for more than 50 percent of start forms in the third quarter.

o
Access outside the U.S. expanded with formal reimbursement in 28 markets and continued revenue growth in the EU, Asia Pacific and Latin America.

·
TEGSEDI (inotersen) – launched in multiple markets for the treatment of polyneuropathy of hereditary transthyretin amyloidosis (hATTR) in adult patients

o
TEGSEDI approved in the U.S., EU and Canada

o
Commercial patients in Germany on TEGSEDI

o
TEGSEDI prescriptions received in the U.S.

·
WAYLIVRA (volanesorsen) – under regulatory review for the treatment of people living with FCS

o
Preparing for launch in the EU following approval

o
Planning to confirm a path forward in the U.S. and Canada

Pipeline and Business Progress

·
Ionis and Akcea reported positive top-line data from a Phase 2 study of AKCEA-APO(a)-LRx in people with high levels of Lp(a) and established cardiovascular disease demonstrating robust target reductions and a favorable safety and tolerability profile
·
Ionis and Roche entered a new collaboration to develop IONIS-FB-LRx for the treatment of people with complement-mediated diseases. Ionis received a $75 million upfront payment and will be eligible for development, regulatory and sales milestone payments and license fees of up to $684 million plus royalties of up to 20 percent on commercial sales
·
Positive Phase 1b/2 data for danvatirsen (IONIS-STAT3-2.5Rx) in combination with durvalumab were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress, demonstrating a response rate approximately double that of durvalumab alone, based on previous studies in patients with refractory head and neck cancer. Ionis earned a $17.5 million milestone payment because AstraZeneca is advancing the program
·
Ionis completed enrollment in a Phase 2b study of IONIS-FXIRx in patients with end-stage renal disease on dialysis, with data planned for mid-2019
·
Ionis or its partners initiated clinical studies with IONIS-GHR-LRx (Phase 2), IONIS-C9Rx (Phase 1/2), IONIS-FXI-LRx and IONIS-AZ4-2.5-LRx (Phase 1)
·
Ionis earned a $10 million milestone payment from AstraZeneca for advancing an undisclosed oncology program into development
·
Ionis appointed Dr. Michael Hayden and Mr. Peter N. Reikes to its Board of Directors

Key Upcoming Events

·
Potential approval and launch of WAYLIVRA in the EU

·
Pivotal program initiation for IONIS-HTTRx in patients with Huntington’s disease

·
Results from up to three Phase 2 studies and four Phase 1 studies

·
Initiations of up to three Phase 2 studies and two Phase 1 studies
The increase in revenue in the first nine months of 2018 compared to the same period in 2017 was primarily due to increasing commercial revenue from SPINRAZA royalties, which increased over 175 percent. Our R&D revenue for the first nine months of 2018 was significant and demonstrates our ability to generate sustainable revenue from our numerous partnerships.

R&D revenue from the amortization of upfront payments increased by $22 million in the first nine months of 2018, compared to the same period in 2017 primarily due to Ionis’ 2018 strategic neurology collaboration with Biogen, which started in the second quarter of 2018. In the fourth quarter of 2018, Ionis will add amortization revenue from its new collaboration with Roche to develop IONIS-FB-LRx.

Ionis’ 2018 R&D revenue from milestone payments was bolstered by two $10 million milestone payments in the third quarter, one from Biogen and one from AstraZeneca, as Ionis’ partnered programs advanced. In the same period of 2017, R&D revenue from milestone payments included $90 million of milestone payments from Biogen for SPINRAZA approval in the EU and Japan. Already in the fourth quarter, Ionis has earned nearly $30 million in milestone payments from AstraZeneca.

Operating Expenses

Operating expenses for the three and nine months ended September 30, 2018 on a GAAP basis were $164 million and $480 million, respectively, and on a pro forma basis were $129 million and $383 million, respectively. These amounts compare to GAAP operating expenses for the three and nine months ended September 30, 2017 of $107 million and $309 million, respectively, and pro forma operating expenses of $86 million and $246 million, respectively. The increases in operating expenses were principally due to higher SG&A expenses as Akcea, Ionis’ affiliate, prepared to commercialize TEGSEDI and WAYLIVRA. The Company’s SG&A expenses also increased due to an increase in fees the Company owed under its in-licensing agreements related to SPINRAZA, as a result of increased SPINRAZA product sales.

Net Income (Loss) Attributable to Ionis Common Stockholders

Ionis reported a net loss attributable to Ionis’ common stockholders of $5 million and $46 million for the three and nine months ended September 30, 2018, respectively, compared to a net loss of $3 million and net income of $3 million for the same periods in 2017, all on a GAAP basis. On a pro forma basis, Ionis reported net income attributable to Ionis’ common stockholders of $30 million and $51 million for the three and nine months ended September 30, 2018, respectively, compared $19 million and $67 million for the same periods in 2017.

At September 30, 2018, Ionis owned approximately 75 percent of Akcea. The shares of Akcea third parties own represent an interest in Akcea’s equity that Ionis does not control. However, because Ionis continues to maintain overall control of Akcea through its voting interest, Ionis reflects the assets, liabilities and results of operations of Akcea in Ionis’ consolidated financial statements. Ionis reflects the noncontrolling interest attributable to other owners of Akcea’s common stock in a separate line called "Net loss attributable to noncontrolling interest in Akcea" on Ionis’ statement of operations. Ionis’ net loss attributable to noncontrolling interest in Akcea for the three and nine months ended September 30, 2018, was $16 million and $41 million, respectively. Ionis’ net loss attributable to noncontrolling interest in Akcea for the three and nine months ended September 30, 2017, was $5 million.

For the three months ended September 30, 2018 and 2017, basic and diluted net loss per share were $0.03 and $0.02, respectively. For the nine months ended September 30, 2018, basic and diluted net loss per share were each $0.33. For the nine months ended September 30, 2017, basic and diluted net income per share were each $0.13. All amounts are on a GAAP basis.

Balance Sheet

As of September 30, 2018, Ionis had cash, cash equivalents and short-term investments of $2 billion compared to $1 billion at December 31, 2017. The increase in Ionis’ cash, cash equivalents and short-term investments was primarily due to the $1 billion Ionis received from Biogen for the 2018 strategic neurology collaboration.

Webcast and Conference Call

Today, at 11:30 a.m. Eastern Time, Ionis will conduct a live webcast conference call to discuss this earnings release and related activities. Interested parties may listen to the call by dialing 877-443-5662 or access the webcast at www.ionispharma.com. A webcast replay will be available for a limited time.

Unum Therapeutics to Present Preclinical Data on a New, Emerging Platform Technology for Solid Tumors at the SITC Annual Meeting

On November 6, 2018 Unum Therapeutics Inc. (NASDAQ: UMRX), reported that the Company will present preclinical data on a new proprietary technology platform called Bolt-On Chimeric Receptor, or BOXR, designed to improve the effectiveness of T cells in solid tumor cancers, at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting taking place November 7-11, 2018 in Washington, D.C (Press release, Unum Therapeutics, NOV 6, 2018, View Source [SID1234530852]).

Unum has generated a large panel of novel bolt-on transgenes, evaluated using a unique screening strategy, and has identified lead candidates most likely to enhance T cell functions in the solid tumor microenvironment. The bolt-on transgenes enhanced immunometabolism or costimulation of both ACTR- and CAR-expressing T cells and significantly improved their function under stringent in vitro and in vivo conditions.

"We are excited by this new platform, which we believe has the potential to further bolster our ACTR technology pipeline, and highlights our innovative approaches to overcome immunosuppressive challenges in solid tumors," said Seth Ettenberg, Unum’s Chief Scientific Officer. "We look forward to continuing to explore the potential of this novel technology by selecting a lead development candidate to bring to patients in need in the clinical setting."

Details on the presentation are as follows:

Presentation Title: Select metabolic and costimulatory bolt-on transgenes enhance chimeric receptor-bearing T cell activity against solid tumors
Presenter:Luke Barron, PhD, Unum Therapeutics
Session Title: Cell-Based Therapies for Solid Tumors
Poster Number: 216
Date & Time: Saturday, November 10th, 12:20-1:50 and 7-8:30pm
Location:Walter E. Washington Convention Center, Hall E

Adaptimmune Reports Third Quarter 2018 Financial Results and Business Update

On November 6, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported financial results for the third quarter ended September 30, 2018, and provided a business update (Press release, Adaptimmune, NOV 6, 2018, View Source [SID1234530851]).

"We have now completed the three dose escalation cohorts of the studies with MAGE-A4 and MAGE-A10, our leading wholly owned programs. The Safety Review Committee has agreed that the higher pre-conditioning regimen and cell doses are tolerable and there were no dose limiting toxicities. These studies will now move into the expansion phase, which allows us to treat patients with up to ten billion cells, without a pre-determined stagger across a broad range of tumor types. We have also continued dosing patients in the AFP study with 100 million cells and anticipate escalating to Cohort 2 in early 2019. We expect to report our next clinical data by no later than our first quarter financial results in May 2019," said James Noble, Chief Executive Officer.

Clinical momentum in wholly owned programs

Ongoing MAGE-A10 and MAGE-A4 studies

· There are three ongoing studies with MAGE-A10 and MAGE-A4 SPEAR T-cells

· Two MAGE-A10 studies: one in non-small cell lung cancer (NSCLC) and a triple tumor study in bladder, melanoma, and head & neck cancers

· A MAGE-A4 basket study in NSCLC, bladder, melanoma, synovial sarcoma, myxoid/round cell liposarcoma (MRCLS), head & neck, ovarian, gastric, and esophageal cancers

· All three studies are first-in-human trials utilizing a modified 3+3 design with escalating target doses of 100 million (Cohort 1), 1 billion (Cohort 2), and 5 billion (Cohort 3) transduced SPEAR T-cells to evaluate safety, including dose limiting toxicities (DLTs)

· The preconditioning regimen in the first two cohorts was cyclophosphamide (600mg/m2/day) and fludarabine (30 mg/m2/day) on days -7, -6 and -5, and an extra day of fludarabine was added to the third cohorts and expansion phases, as clinical and translational data indicate that this extra day may be important for optimal T-cell expansion post-infusion

· Following the initial three cohorts, the Safety Review Committee (SRC) meets to decide whether to progress to the expansion phase, which has a target dose of 5 billion cells (range 1.2 to 10B) without pre-determined intervals between patient dosing

· The SRC recommended moving into the expansion phase for the MAGE-A10 triple tumor and MAGE-A4 basket studies

· As in the first two cohorts of these studies, there was no evidence of toxicity related to off-target binding or alloreactivity in the third cohorts at target doses of 5 billion cells

· Most adverse events were consistent with those experienced by cancer patients undergoing chemotherapy or other immunotherapies

ESMO data

· Initial safety data from the first two cohorts of the MAGE-A10 and MAGE-A4 studies were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress (https://bit.ly/2PdB3CR)

· In brief, these data showed:

· Disease progressed for all eight patients treated in the first dose cohorts of the two MAGE-A10 studies (five patients with lung cancer, two with head & neck cancer, and one with melanoma)

· For the three patients treated in Cohort 2 of the MAGE-A10 study (all lung cancer patients), one patient died of pneumonia (unrelated to therapy) and two had stable disease (SD), albeit transient

· Of the six patients treated in Cohorts 1 and 2 of the MAGE-A4 basket study, best response was SD in four patients and progressive disease (PD) in two patients

·One patient in the MAGE-A4 basket study with SD had an overall 27% reduction of target lesions observed at Week 6, and was assessed as PD at the time of the second scan, which took place after the ESMO (Free ESMO Whitepaper) poster cut-off date

· No evidence of toxicity related to off-target binding or alloreactivity at target doses of 100 million or 1 billion cells

· Most adverse events consistent with those experienced by cancer patients undergoing chemotherapy or other immunotherapies

· Transduced cells detectable in peripheral blood at levels consistent with dose

Data from ongoing AFP study

· Dosing in Cohort 1 of AFP study is ongoing

· Anticipate dose escalation to Cohort 2 in early 2019.

NY-ESO data updates to be presented at SITC (Free SITC Whitepaper)

·The NY-ESO program transitioned to GSK in July 2018

·An abstract summarizing NY-ESO SPEAR T-cells in MRCLS was accepted for presentation at SITC (Free SITC Whitepaper), and is available online today

· Data in the abstract state that out of ten MRCLS patients, there were four with partial responses (PRs) and four with SD, as per investigator assessment

· These data will be updated in a poster at SITC (Free SITC Whitepaper)

· Overall, there was evidence of reduction in target lesions in seven patients out of eight evaluable patients

· The data submitted in the abstract included investigator assessments. These assessments showed a best response of four confirmed PR, one unconfirmed PR, and three patients with SD out of eight evaluable patients

· Two of the responses were confirmed before the minimum 28 days required by RECIST v1.1 (22 and 25 days), and the patients subsequently progressed

· Therefore, the response rate by RECIST, which will be presented in the poster, is two confirmed PRs and six patients with SD out of the eight evaluable patients

· Patients in the MRCLS study received the same preconditioning regimen as was used in Cohort 4 of the synovial sarcoma study, and these patients had less durable responses compared to Cohort 1 patients in the synovial sarcoma study, who received a more intense preconditioning regimen

· The most frequent AEs were consistent with those experienced by patients with cancer who are undergoing cytotoxic chemotherapy or other immunotherapies

· A second poster with NY-ESO data will also be presented at SITC (Free SITC Whitepaper) summarizing translational research conducted in the context of the NY-ESO synovial sarcoma study examining serum factors that lead to T-cell expansion with different preconditioning regimens (including the impact of fludarabine), tumor micro-environment analyses pre- and post-infusion, and SPEAR T-cell functionality post-infusion. This abstract is also available online.

Manufacturing

Adaptimmune on its way to becoming a fully integrated cell therapy company

· 2018 has been a successful year for manufacturing with the Navy Yard facility regularly producing target cell doses > 1 billion cells with more than 50% producing > 5 billion cells

· Producing cell doses across multiple solid tumor indications

· Cells have been manufactured for a number of patients who could enter the MAGE-A4 and/or MAGE-A10 expansion phases, once eligible

Other corporate news

Adaptimmune is focused on its next stage of development and in a strong position to deliver success with SPEAR T-cell therapies

· Announced the closing of a registered direct offering of Adaptimmune’s American Depositary Shares ("ADSs") (https://bit.ly/2MZFEIH) with net proceeds of approximately $100 million

· Adaptimmune intends to use the net proceeds from this offering to advance the Company’s wholly owned pipeline of SPEAR T-cell candidates through clinical trials as well as for other general corporate purposes

· Completed transition of NY-ESO IND to GSK and received approximately $26 million in milestone payments

· Funded through to late 2020 with cash and cash equivalents of $153.1 million and total liquidity(1) of $237.7 million

· Held annual Scientific Advisory Board meeting in October with Adaptimmune R&D leaders and external experts in immunology and oncology (bios available here: https://bit.ly/2PvHH4w); focused on optimal employment of NY-ESO learnings in ongoing and future studies as well as strategies for novel target identification

Financial Results for the three and nine month period ended September 30, 2018

· Cash / liquidity position: As of September 30, 2018, Adaptimmune had cash and cash equivalents of $153.1 million and Total Liquidity(1) of $237.7 million.

· Revenue: Revenue for the three and nine months ended September 30, 2018 was $40.8 million and $58.0 million, respectively, compared to $27.2 million and $33.6 million for the same periods of 2017. The revenue in the three and nine months ended September 30, 2018 includes $39.1 million of revenue for the license to NY-ESO, which commenced in September 2018.

· Research and development ("R&D") expenses: R&D expenses for the three and nine months ended September 30, 2018 were $23.5 million and $75.5 million, respectively, compared to $24.0 million and $62.2 million for the same periods of 2017. The R&D expenses in the nine months ended September 30, 2018 has increased compared to the same period in 2017 due to increased clinical trial and related manufacturing activities. R&D expenses in the three months ended September 30, 2018 compared to the same period in 2017 decreased due to the transfer of the NY-ESO program to GSK.

· General and administrative ("G&A") expenses: G&A expenses for the three and nine months ended September 30, 2018 were $10.3 million and $32.8 million, respectively, compared to $8.1 million and $22.3 million for the same periods of 2017. The increase was primarily due to increased personnel costs consistent with the Company’s planned infrastructure growth.

· Other (expense) income, net: Other expense for the three and nine months ended September 30, 2018 was $2.2 million and $10.5 million, respectively, compared to an income of $3.6 million and $7.2 million for the same periods of 2017. Other income primarily comprises unrealized foreign exchange gains, which fluctuate depending on exchange rate movements and the amount of foreign currency assets and liabilities.

· Net income (loss): Net income (loss) attributable to holders of the Company’s ordinary shares for the three and nine months ended September 30, 2018 was an income of $5.2 million and a loss of $59.3 million, respectively, ($0.01 and $(0.10) per ordinary share) compared to a loss of $0.9 million and $42.9 million, respectively, ($(0.00) and $(0.08) per ordinary share) in the same periods of 2017.

(1) Total liquidity is a non-GAAP financial measure, which is explained and reconciled to the most directly comparable financial measures prepared in accordance with GAAP below.

Financial guidance

The Company believes that its existing cash, cash equivalents and marketable securities will fund the Company’s current operations through to late 2020.

Conference call information

The Company will host a live teleconference and webcast at 8:00 a.m. EST (1:00 p.m. GMT) today. The live webcast of the conference call will be available via the events page of Adaptimmune’s corporate website at www.adaptimmune.com. An archive will be available after the call at the same address. To participate in the live conference call, please dial (833) 652-5917 (U.S.) or +1 (430) 775-1624 (International). After placing the call, please ask to be joined into the Adaptimmune conference call and provide the confirmation code (2458438).