Biotech Week Ahead, June 3

Biotech stocks came under pressure this week ahead of the ASCO 2019 presentations. Headlines on legal woes related to the opioid crisis and drug price manipulation led to weakness in some stocks.

The unfolding week is all about the presentations at one of the largest educational and scientific events for the oncology community.

Here are the key events/catalysts to look forward to:

Conferences

• The American Society of Clinical Oncology, or ASCO, 2019 Annual Meeting – May 31–June 4, in Chicago, Illinois
• The European Academy of Allergy and Clinical Immunology 2019 Annual Congress – June 1-5, in Lisbon, Portugal
• 20th Global Nephrologists Annual Meeting – June 3-4, in London
• Jefferies 2019 Healthcare Conference – June 4-7, in New York City
• European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2019 Annual Meeting – June 5-8, in Glasgow, Scotland
• HBV Cure Meeting – June 7-8, in Singapore
• The American Diabetes Association’s 79th Scientific Sessions – June 7-11, in San Francisco, California

PDUFA Dates

The FDA is scheduled to rule Monday on Merck & Co., Inc. MRK 0.61%‘s sNDA for Zerbaxa (ceftolozone and tazobactam) in treating adult patients with ventilated nosocomial (hospital-acquired) pneumonia

ASCO Presentations On Sunday, June 2

• Aduro BioTech Inc ADRO 4.84% – Phase 1b data for ADU-S100 and Spartalozumab (solid tumors or lymphomas)
• Celgene Corporation CELG 0.82% – Phase 1/2 data on CC-220 (relapsed and/or refractory multiple myeloma)
• CAN-FITE BIOPHA/S ADR CANF 1.33% – already-released Phase 2 data for Namodenoson (second-line treatment of advanced liver cancer)
• Amgen, Inc. AMGN 1.38% – Phase 1 data for AMG 420 (relapsed, refractory multiple myeloma)
• ZIOPHARM Oncology Inc. ZIOP 3.6% – Phase 1 data for Ad-RTS-Hil-12 (recurrent glioblastoma) as well as initial Phase 1 data for Ad-RTS-Hil-12 plus veledimex in combination with Bristol-Myers Squibb Co BMY 1.16%‘s Opdivo (refractory glioblastoma multiforme)
• VBI Vaccines Inc VBIV 4.04% – Phase 1/2a expanded Part A data for VBI-1901 in recurrent glioblastoma multiforme
• Puma Biotechnology Inc PBYI 2.19% – additional Phase 2 data for Neratinib monotherapy with high dose loperamide prophylaxis (extended adjuvant treatment of early-stage HER-2 positive breast cancer)
• AstraZeneca plc AZN 0.36% and Merck – already-released Phase 3 data for Lynparza (pancreatic cancer)

ASCO Presentations On Monday, June 3

• Blueprint Medicines Corp BPMC 2.93% – updated Phase 1 data for BLU-667 (RET-altered solid tumors)
• Actinium Pharmaceuticals Inc ATNM 10.3% – Phase 3 data for Iomab-B (hematopoietic stem cell transplantation)
• Amgen – Phase 1 data for AMG510 (solid tumors)
• Agios Pharmaceuticals Inc AGIO 2.66% – updated Phase 1 data for Ivosidenib (IDH1 mutant newly diagnosed AML ineligible for standard therapoes) as well as updated Phase 1 data for Ivosidenib in combination with Vidaza for newly diagnosed AML with an IDH1 mutation) and Phase 1 data for Ivosidenib and Vorasidenib (IDHm low-grade glioma)
• Incyte Corporation INCY 0.17% and Novartis AG NVS 0.22% – already-released Phase 2 data for INC280 (non-small cell lung cancer)
• Forty Seven Inc FTSV 9.94% – Phase 1b data for 5F9 in AML as well as Phase 1b data for 5F9 + Azacitidine in AML
• Incyte – Poster presentation of Phase 2 data for INCB54828 (cholangiocarcinoma)
• Corcept Therapeutics Incorporated CORT 2.2% – Phase 1/2 data for relacorilant plus Arbaxane (solid tumors)
• Seattle Genetics, Inc. SGEN 3.95% – full Phase 2 data for enfortumab vedotin (urothelial cancer)
• MEI Pharma Inc MEIP 3.05% – Phase 1b data for ME-401 (relapsed/refractory follicular lymphoma/chronic lymphocytic leukemia)
• Constellation Pharmaceuticals Inc CNST 1.41% – interim Phase 2 data for CPI-060 and ruxolitinib (myelofibrosis)
• Stemline Therapeutics Inc STML 1.65% – Phase 2 data for SL-401 (chronic myelomonocytic leukemia)
• Nektar Therapeutics NKTR 2.46% – Phase 2 data for NKTR-214 and Opdivo (sarcomas)
• Stemline Therapeutics & Epizyme Inc EPZM 1.58% – updated Phase 2 data for Tazemetostat (epithelial sarcoma)

ASCO Presentations On Tuesday, June 4

• Roche Holdings AG Basel ADR RHHBY 0.51% – Phase 3 overall survival data for Tecentriq plus nab-paclitaxel (triple-negative breast cancer)
• MacroGenics Inc MGNX 4.68% – detailed Phase 3 data for Margetuximab (metastatic breast cancer)
• Roche & AbbVie Inc ABBV 1.15% – Phase 3 data for Venclexta plus Gazyva (chronic lympocytic leukemia)
• Celgene – updated Phase 1 data for Liso-cel (chronic lymphocytic leukemia)
• Puma Biotech – already-released Phase 3 data for Neratinib (third-line HER2-positive metastatic breast cancer)
• Atara Biotherapeutics Inc ATRA 2.68% – Phase 1 data for autologous T cells (malignant pleural disease)
• TG Therapeutics Inc TGTX 3.09% – Phase 2/3 MZL cohort data for TG-1101 and TGR-1202 (non-Hodgkin lymphoma)

Other Presentations

AnaptysBio Inc ANAB 2.69% is due to present on Wednesday Phase 2a data for ANB020 in severe adult eosinophilic asthma at the European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2019 annual meeting.

Spring Bank Pharmaceuticals Inc SBPH 4.79% will present full data for Inarigivir 400mg in healthy volunteers at the HBV Cure Meeting

Opko Health Inc. OPK 2.7% is scheduled to present already-released Phase 2b topline data for OPK88003 in obesity and diabetes at the American Diabetes Association’s 79th Scientific Sessions.

Albireo Pharma Inc ALBO 0.09% is set to present on June 7 Phase 2 data for Odevixibat in biliary atresia at the European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2019 annual meeting

IPO Quiet Period Expiry

Axcella Health Inc AXLA 0.14%

Cortexyme Inc CRTX 2.1%

NextCure Inc NXTC 2.87%

Milestone Pharmaceuticals Inc MIST 2.32%

Applied Therapeutics Inc APLT 0.5%

https://www.benzinga.com/general/biotech/19/06/13834066/the-week-ahead-in-biotech-asco-presentations-pick-up-the-pace

CVS Health Mounts Defense of Aetna Deal on Two Fronts

CVS Health Corp. will defend its acquisition of insurer Aetna Inc. in two high-profile settings Tuesday, seeking to sell skeptical investors and a federal judge on the nearly $70 billion deal.

CVS lawyers will be in a Washington, D.C., federal court for the start of an unusual three-day proceeding in which U.S. District Judge Richard Leon is considering whether the Justice Department adequately protected competition when it approved the deal last year.

In New York, the Woonsocket, R.I.-based health-care company will hold an investor day to discuss its outlook, with analysts looking for evidence that CVS can improve its financial performance amid challenges to its core businesses.

The deal, reached in November, combined CVS’s sprawling network of pharmacies and pharmacy-benefit-management business with Aetna’s health-plan assets. Coming together, the companies had sketched a vision of lowered health-care costs and improved care for consumers.

A CVS spokesman declined to comment on the investor day or the court hearing.

The Justice Department’s antitrust division approved the merger after the companies agreed to sell off Aetna’s Medicare Part D drug business to WellCare Health Plans Inc. The department said the divestiture was needed because Aetna and CVS had been important competitors in selling Medicare drug plans to seniors in 22 states.

Groups like the American Medical Association said the divestiture didn’t do enough to protect competition for prescription-drug plans, and they argued the department didn’t address broader concerns about health-care industry consolidation.

The criticism caught the attention of Judge Leon, who is considering whether to approve the settlement between the companies and the Justice Department. Judges typically give the nod to such settlements as a matter of routine — and without extended consideration — but Judge Leon made clear he has concerns about the deal, and he took the unprecedented move of scheduling three days of hearings with live witness testimony.

The judge insists that the proceedings aren’t a mini-trial of a merger that the government isn’t seeking to block, saying the testimony would help him determine whether the settlement is in the public interest.

Judge Leon, a George W. Bush appointee, said he would hear from six witnesses: three critical of the merger and three selected by CVS to testify in favor of the deal, including executives from CVS and Aetna.

For its part, the Justice Department said in a May 24 filing that Judge Leon’s rules for the proceedings were unfair because the company could neither present its own witnesses nor cross-examine those critical of the settlement. Judge Leon said his procedures were appropriate, rejecting what he described as the department’s “11th-hour request” to change them.

It isn’t clear what would happen next should the judge reject the Justice Department settlement allowing the merger. Meantime, CVS is moving forward as if the court proceedings won’t impact its business. The company already has sold the assets to WellCare that the Justice Department required, and it has contractual obligations to provide support to WellCare through 2019, regardless of whether the court formally approves the agreement.

CVS faces challenges that have affected its rivals as well, including a squeeze on pharmacy margins and government scrutiny of the traditional pharmacy-benefits business model, particularly rebates paid by drugmakers. Health insurers’ shares have also been dragged down by some Democrats’ support for universal government health coverage. There were “pressures on all the legacy businesses that accelerated heading into this year,” said Matthew Borsch, an analyst with BMO Capital Markets.

In February, CVS gave a downbeat earnings projection for 2019, pushing its shares down sharply and leading investors to press for more detail about the company’s growth plans. The shares have remained stagnant, despite stronger-than-expected first-quarter results, and CVS has promised a fuller picture of its future in the Tuesday session.

A JPMorgan Chase & Co. poll of investors found their highest priorities for the CVS investor day were long-term financial guidance and a clear strategic vision. Among respondents who didn’t own CVS shares, a third said the session might convince them to buy. “Their credibility can be restored based on their ability to lay out the strategy and numbers,” said Lisa Gill, a JPMorgan analyst.

Analysts polled by Refinitiv were projecting earnings per share of $5.02 in 2019, $5.66 in 2020 and $6.67 in 2021. On an adjusted basis, they predicted earnings per share of $6.85 for 2019, a 5.4% increase to $7.22 for next year and growth of 8% to $7.80 for 2021.

“It’s really about operating earnings and their ability to grow that,” said Kevin Caliendo, an analyst with UBS.

Investors are also looking for specifics around CVS’s plans to build up its health-care role in the wake of the merger, say analysts, including through new health hub stores designed to offer a broader range of services, many aimed at those with chronic illnesses. Problem areas such as the company’s troubled Omnicare long-term-care pharmacy business are also likely to draw questions, they said.

https://www.marketscreener.com/CVS-HEALTH-CORPORATION-12230/news/CVS-Health-Mounts-Defense-of-Aetna-Deal-on-Two-Fronts-28693448/

Alzheimer’s-Cholesterol Connection

Elevated low density lipoprotein (LDL) cholesterol levels were tied to a higher probability of early-onset Alzheimer’s disease, a case series showed.

Early-onset Alzheimer’s patients had higher LDL cholesterol, total cholesterol, and apolipoprotein B (Apo B) levels, even after adjusting for the apolipoprotein E ε4 (APOE E4) allele — a genetic risk factor known to raise circulating cholesterol — reported Thomas Wingo, MD, of Emory University in Atlanta, and colleagues.

Moreover, early-onset Alzheimer’s cases were strongly associated with rare variants of APOB, which codes for the major protein of LDL cholesterol, they wrote in JAMA Neurology.

“A big question is whether there is a causal link between cholesterol levels in the blood and Alzheimer’s risk,” Wingo told MedPage Today. “The existing data is murky on this point.”

“Our current work is focused on testing whether there is a causal link,” he continued. “If there is a causal link between Alzheimer’s disease and cholesterol, we might need to revise targets for LDL cholesterol to help reduce Alzheimer’s risk.”

Early-onset Alzheimer’s occurs before age 65 and has a large genetic basis with heritability of 91% to 100%. Mutations in three genes that cause Alzheimer’s — amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) — were discovered in families with early-onset disease, but most likely account for less than 10% of incident cases.

In this analysis, Wingo and colleagues studied three potential causes of early-onset Alzheimer’s: Alzheimer’s genetic variants, circulating plasma lipoproteins, and APOB, which is known to harbor rare variants with strong effects on raising or lowering LDL cholesterol.

To collect this data, they sequenced APOB, APP, PSEN1, and PSEN2 in samples from 2,125 early-onset cases and controls recruited from 29 Alzheimer’s disease research centers from 1984 through 2015. They also measured plasma cholesterol levels in 267 frozen samples collected from early-onset Alzheimer’s patients and controls from 2009 to 2014 at Emory University and the University of California San Francisco Alzheimer’s research centers.

Of the 2,125 samples that underwent genetic sequencing, 1,276 were from women (60.0%) and 654 (30.8%) were from patients with early-onset Alzheimer’s. The average age of early-onset patients was 55.6 and the average age of controls was 72.

In this group, only 3.4% carried APP, PSEN1, and PSEN2. The APOE E4 allele — the largest known genetic risk factor for late-onset Alzheimer’s — accounted for 10.1% of the variance. “These results collectively confirm that these four genes account for only a minority of the strong genetic predisposition seen in early onset Alzheimer’s disease, and additional genes are likely to be involved,” noted Makoto Ishii, MD, PhD, of Weill Cornell Medicine in New York City, in an accompanying editorial.

After controlling for APOE E4, early-onset cases had higher levels of total cholesterol (mean difference 21.9 mg/dL, P=2.9 × 10^-5), LDL cholesterol (mean difference 22.0 mg/dL, P=1.8 × 10^-6), and Apo B (mean difference 12.0 mg/dL, P=2.0 × 10^-6) than controls in the 267 plasma samples. Adjusting for age showed similar results.

Deep resequencing showed that rare APOB coding variants were significantly more abundant in early-onset Alzheimer’s cases, after taking sex, APOE E4, genetic principal components, and study center into account (effect size 0.20; P = 4.20 × 10^-4).

“Overall, this is an important study that provides the first evidence that rare genetic coding variants of APOB are strongly associated with early-onset Alzheimer’s disease,” Ishii observed. Consistent with these findings, a transgenic mouse model overexpressing APOB had significant memory impairment and increased beta-amyloid levels compared with wild-type mice, he noted.

“However, previous studies measuring circulating apolipoprotein B levels in humans have been inconclusive, with a large population study finding no association between circulating apolipoprotein B levels and incident dementia or Alzheimer’s disease,” he continued. “Therefore, whether these findings can be verified in individuals with late-onset Alzheimer’s disease remains to be determined.”

The study suggests other contributing factors — possibly rare variants in other genes involved directly in LDL cholesterol metabolism — may be involved, Ishii added. And while this analysis focused on cholesterol, “similar studies investigating other cerebrovascular risk factors, such as insulin resistance or type 2 diabetes mellitus in individuals with early-onset Alzheimer’s disease, may be equally enlightening,” he wrote.

The findings generate a number of questions, including whether APOB has protective and deleterious variants and what role APOB variants may play in late-onset Alzheimer’s disease, noted Wingo and colleagues.

The analysis also has several limitations, they noted. It does not infer causality and because of the rarities of the alleles tested, could not be analyzed using Mendelian randomization. Cholesterol data may be confounded by Alzheimer’s severity, smoking, or cholesterol-lowering drugs, but the genetic link between APOB and early-onset Alzheimer’s is unlikely to be affected by these variables, they added.

The study was supported by the Veterans Health Administration, the NIH, the Emory Integrated Genomics Core, the To Remember Foundation, the Douglas French Alzheimer’s Foundation, and the State of California Department of Health Services, Alzheimer’s Disease Research Center of California.

Researchers disclosed relevant relationships with the NIH, the NIA, the VA, Avid Radiopharmaceuticals, Eli Lilly, Piramal Imaging, GE Healthcare, Eisai, Axon Neuroscience, Merck, Genentech, Roche, Quest Diagnostics’ Dementia Pathway Collaboration, Cornell University, the Bluefield Project, Avanir Pharmaceuticals, AbbVie, Novartis, Biogen, Cognito Therapeutics, Future Health, and Takeda.

Editorialist Ishii was supported by the NIH and owns stock in Regeneron Pharmaceuticals.

Primary Source

JAMA Neurology

Source Reference: Wingo TS, et al “Association of early-onset Alzheimer disease with elevated low-density lipoprotein cholesterol levels and rare genetic coding variants of APOB” JAMA Neurol 2019; DOI: 10.1001/jamaneurol.2019.0648.

Secondary Source

JAMA Neurology

Source Reference: Ishii M “Apolipoprotein B as a new link between cholesterol and Alzheimer disease” JAMA Neurol 2019; DOI: 10.1001/jamaneurol.2019.0212.

Comments

NIR TSABAR

June 1, 2019

Parallel lines don’t meet.. Only randomized controlled trials (RCTs) can tell us whether any i n t e r v e n t i o n to lower cholesterol will benefit humans in fighting Alzheimer’s disease. Since LDL is a known physiologic vehicle of our organism to deliver metabolites needed for cell functions, and since our normal brains contain lots of lipids and cholesterol, and since statin RCTs repeatedly failed in preventing dementia, and since loss of memory or depression are side effects of statins – this line of intervention will probably won’t work.

Gary DeBacher

June 2, 2019

It is time to stop looking for causes and to start treating. There has long been evidence that low-dose lithium prevents ADL, and can reverse it in its early stages. Cannabidiol promises to replace lithium as a method to clear amyloid and tau from the hippocampus, and to provide strong general neuroprotection.

I agree entirely with the previous commenter.

https://www.medpagetoday.com/neurology/alzheimersdisease/80108

Iovance therapy appears safe, effective in melanoma, cervical cancer

Data from two trials evaluating the safety and efficacy of adoptive cell transfer with autologous tumor-infiltrating lymphocytes showed promising overall response rates for the treatment of advanced metastatic melanoma and cervical cancer, according to results presented at ASCO Annual Meeting.

The study data show that investigational therapy LN-144 (lifileucel; Iovance Biotherapeutics) had a 38% overall response rate in patients with advanced metastatic melanoma. Investigational therapy LN-145 (Iovance Biotherapeutics) conferred a 44% ORR in patients with advanced cervical cancer.

Both trials used an identical treatment method that involve isolating a patient’s tumor-infiltrating lymphocytes (TILs) from a resected portion of their tumor, and then multiplying them in a laboratory. The manufacturing process takes 22 days.

Patients in both trials received lymphodepletion for 1 week with cyclophosphamide or fludarabine and were given up to six doses of interleukin-2 after the infusion of LN-144/LN-145.

“Taking the tumor out of the patient allows us to grow these lymphocytes to a far greater number,” Amod Sarnaik, MD, surgical oncologist with the Melanoma Center of Excellence at Moffitt Cancer Center and lead author of the LN-144 study, told HemOnc Today.

“These patients are treatment refractory, so their disease has progressed on the best FDA-approved treatments that are available,” he said. “Our treatment has a 38% response rate. You can walk around the ASCO exhibit hall and you are not going to find very many, if any, treatments that can match that response rate.”

There are few effective treatment options for patients with advanced cervical cancer, according to Amir Anthony Jazaeri, MD, vice chair for clinical research and the director of the Gynecologic Cancer Immunotherapy Program in the department of gynecologic oncology and reproductive medicine at The University of Texas MD Anderson Cancer Center.

“It’s nice to have a process that’s only 22 days, because these are patients with metastatic disease and if they wait too long, they can experience progression,” Jazaeri told HemOnc Today.

He explained that the entire process takes about 2 weeks, from the start of lymphodepletion, followed by TIL infusion, ending with adjuvant interleukin-2 therapy.

TILs for metastatic melanoma

In the phase 2, open-label, multicenter clinical trial, 66 patients (median age, 55 years; 59% men)with stage IIIC or stage IV metastatic melanoma were infused with cryopreserved lifileucel (mean cells infused, 27.3 × 10⁹).

Patients had received a mean of 3.3 previous therapies (range, 1-9) before infusion, including PD-1 inhibitors (100%), CTLA-4 inhibitors (80%) and BRAF/MEK inhibitors (23%). Study patients also had a high baseline tumor burden (106 mm mean target lesion sum of diameters).

https://www.healio.com/hematology-oncology/melanoma-skin-cancer/news/online/%7B245df162-58bc-4225-b446-a92498423403%7D/tumor-infiltrating-lymphocyte-therapy-appears-safe-effective-in-melanoma-cervical-cancer

ASCO: Sanofi’s anti-CD38 myeloma combo ups responses, extends lives

Sanofi’s anti-CD38 antibody isatuximab added to the standard of care for relapsed multiple myeloma extended patients’ lives and nearly doubled the number of patients for whom the standard of care worked. The phase 3 data, presented Sunday at the annual meeting of the American Society of Clinical Oncology, showed that the isatuximab combination shrank tumors in 60% of patients compared to 35% of patients taking the standard of care alone.

The standard of care is a combination of Celgene’s Pomalyst (pomalidomide) and the corticosteroid dexamethasone—dubbed pom-dex—which is usually given to patients who have relapsed after undergoing multiple treatments.

“Myeloma patients go through a journey where they get treated, they go into remission, and then they relapse, get treated and go into remission,” Sanofi R&D head John Reed told FierceBiotech. “[Pom-dex] is usually the third line, when they’ve already been through this a couple times—by the time the third relapse occurs, there’s not much to offer patients.”

Frontline treatments succeed in the majority of patients, but multiple myeloma is still considered incurable—“everybody eventually relapses,” Reed said. Sanofi is working on isatuximab as an agent that can boost the efficacy of multiple myeloma treatments at various stages of the disease.

The phase 3 study enrolled 307 patients in 24 countries with relapsed or refractory multiple myeloma who had received at least two prior therapies. They received either pom-dex alone or pom-dex in tandem with isatuximab.

The isatuximab combo kept cancer at bay for a median of 11.5 months, a five-month improvement over the 6.5 months for pom-dex alone. It also increased the number of patients for whom pom-dex worked—the combo shrank tumors in 60% of patients, compared to 35% for the standard of care alone. What’s more, of the patients who responded to treatment, the isatuximab combo worked faster, taking a median of 35 days to get a response versus 58 days for pom-dex alone.

“Isatuximab in combination with pomalidomide and dexamethasone resulted in an impressive 40% reduction in the risk of progression or death compared to pomalidomide and dexamethasone alone,” said the study’s principal investigator, Paul Richardson, M.D., in a statement. “This outcome is noteworthy because this trial included a particularly difficult-to-treat, relapsed and refractory patient population that was, in my view, highly reflective of real-world practice.”

An analysis showed that the isatuximab combo performed similarly in different subgroups, including the elderly and people with poor kidney function.

“It gives you real confidence in the robustness of the data that every subgroup we looked at, you saw that adding isatuximab provided additional benefit,” Reed said. “When you see data sets where some groups benefit and others don’t, you wonder how strong are these data?”

Isatuximab showed early promise as a single agent, but Sanofi felt it would be best used to improve existing cancer treatments. It is testing it alongside earlier-line treatments such as Takeda’s Velcade and Amgen’s Kyprolis and is thinking about combining it with experimental treatments like the bispecific antibody it’s working on with Regeneron, Reed said.

Sanofi has filed isatuximab for approval in the U.S. and Europe and doesn’t expect any hiccups with the regulators, Reed said.

“We should be a player in myeloma pretty soon—that gives us an anchor point around which to build. Certainly, building vertically within myeloma—going to first-, second- and third-line therapy—[will involve] bringing in novel combination partners, so there will be a quite robust effort there.”

Isatuximab, like Johnson & Johnson’s blockbuster Darzalex (daratumumab) targets the CD38 receptor found on multiple myeloma cells to attack the cancer. Sanofi thinks it could one-up its rival thanks to a different different mechanism.

“Isatuximab binds to a different epitope on the CD38 target than daratumumab and in the laboratory, you can show mechanistic differences and how that affects the attack on the tumor,” Reed said.

“Isatuximab … induces a direct cell suicide signal in the myeloma cell, which is something daratumumab doesn’t do,” he said. “Also, CD38 is an enzyme and has what is called ecto-enzyme activity, where the enzyme activity is on the surface of the cell, not the interior of the cell.” Isatuximab blocks this activity strongly while Darzalex does so weakly, Reed said. Sanofi believes this combats the production of metabolites by the cell that tamp down the immune system in the tumor microenvironment.

Of course, Reed said, it isn’t an apples-to-apples comparison and Sanofi will need to replicate the success of isatuximab in the lab into patients in the clinic. But if it works, it will be a success story for Sanofi’s efforts to build more of its pipeline from internal research rather than through partnerships.

https://www.fiercebiotech.com/biotech/asco-sanofi-s-anti-cd38-combo-boosts-responses-extends-lives-advanced-multiple-myeloma

Gates, Bezos-backed Alzheimer’s accelerator issues first awards

The Alzheimer’s Drug Discovery Foundation (ADDF) has selected the first four research ideas to be funded through its Diagnostics Accelerator program aimed at developing new tools and biomarkers for the disease and its related dementias.

Backed by some of the richest people in the world—including Bill Gates, Jeff and MacKenzie Bezos and ADDF co-founder Leonard Lauder—the accelerator program plans to award up to $50 million over the next three years. It expects to spend up to $10 million this year on at least 10 projects, with the first four totaling up to about $3.5 million.

The accelerator sent out an additional request for proposals for digital tests and biomarkers this April and plans to issue those awards before the end of the year. The first set of awardees focuses on cheaper, scalable diagnostics such as blood tests and eye scans.

“Unlike heart disease and cancer, we lack simple and cost-effective diagnostic tools and biomarkers that are critical to finding ways to prevent and treat Alzheimer’s disease,” Howard Fillit, the foundation’s executive director and chief science officer, said in a statement.

“Once we have them, we will better understand how Alzheimer’s progresses and make clinical drug trials more efficient and rigorous,” Fillit said.

The projects include a grant of up to $2 million to Amoneta Diagnostics and its chief scientific officer, Saliha Moussaoui. Amoneta based in France, just north of Basel, Switzerland, is developing a liquid biopsy to predict mild cognitive impairment and early Alzheimer’s, by measuring two types of RNAs that are stable in the bloodstream.

Researchers at the University of Gothenburg in Sweden working under Professor Kaj Blennow will receive $500,000 for their work on a blood test aimed at detecting brain-derived tau protein fragments similar to the ones found in the cerebrospinal fluid.

University of Edinburgh research fellow Tom MacGillivray and his lab, meanwhile, will get nearly $490,000 to develop their retinal biomarkers to help track neurodegeneration and changes in the eye’s vasculature, using a cloud-based system for analyzing images.

Associate Professor Peter van Wijngaarden of the Centre for Eye Research Australia, through the University of Melbourne, will get just over $420,000 to examine a simplified eye scan to detect amyloid in the retina ahead of cognitive decline. His team is also developing a more portable and inexpensive camera that aims to replace PET imaging or invasive fluid tests and biopsies.

https://www.fiercebiotech.com/medtech/gates-and-bezos-backed-alzheimer-s-accelerator-issues-first-diagnostic-development-awards

ASCO: AZ, Merck’s Lynparza in pancreatic cancer halves progression risk

AstraZeneca and Merck’s Lynparza is on a roll when it comes to making headlines at the American Society of Clinical Oncology (ASCO) annual meeting—and doing it in some of the toughest-to-treat cancers out there. And it wasn’t going to stop this year.

Sunday, the drugmakers trumpeted phase 3 data showing the PARP inhibitor slashed the risk of disease worsening or death by 47% in patients with germline BRCA-mutated pancreatic cancer that hadn’t progressed after an initial round of chemo. Lynparza patients in the study, dubbed Polo, went a median 7.4 months without their cancer advancing compared with just 3.8 months for placebo patients.

At the one-year mark, Lynparza had kept cancer at bay for 34% of patients versus placebo’s 15%. And at the two-year mark, Lynparza continued the trend, staving off progression in more than twice as many patients as placebo did—at 22% and 10%, respectively.

The results are “very exciting” considering “we are now able to offer a chemo-free option in maintenance to patients who for over a decade haven’t had any meaningful improvement,” Dave Fredrickson, executive vice president and global head of AstraZeneca’s oncology business unit, said.

Pancreatic cancer has been a tough nut for drugmakers to crack, in part because companies haven’t had a target to go after in development—until now.

“In the absence of those, chemotherapy becomes your only option, which is not a great option for patients relative to … other tools we have at our disposal in other tumor types,” Fredrickson said, adding “this will absolutely redefine the standard of care for gBRCA pancreatic cancer.”

And the results will change something else, too, he predicts. “What this will do, assuming it’s approved, is create the imperative to make sure we’re testing for BRCA outside of just women’s cancers,” he said. The company has plenty of experience at driving new testing habits, he noted, including with Lynparza in BRCA-mutated ovarian cancer.

“I have every confidence that … in a disease that is as difficult to treat as pancreatic cancer, we will be able to work together with the community” to increase testing, and “I believe that once we know that patients are gBRCA, it should be very clear that they should be treated with Lynparza,” Fredrickson said.

In the last three years, Lynparza has ranked among ASCO’s biggest newsmakers with data from three separate disease areas. Last year, it made waves with a Zytiga combo in prostate cancer, and the year before, it posted big survival numbers in breast cancer.

https://www.fiercepharma.com/pharma/embargoed-til-sunday-6-2-at-730-am-et-az-merck-s-lynparza-nearly-halves-pancreatic-cancer