Philips Shares Slump on Profit Warning and Sleep Apnea Device Writedown

 Philips shares fell to their lowest in a decade on Wednesday as the Dutch health tech company said supply chain problems would hit sales, and wrote down 1.3 billion euros ($1.26 billion) of the value of its sleep apnea business.

Shares were down 9% at 0750 GMT at 14.13 euros, hitting their lowest level since June 2012.

In its second profit warning of the year, Philips said third-quarter core profit would drop around 60%, as ongoing supply chain problems had pushed down comparable sales by around 5%.

Philips said problems with supply shortages had been much greater than anticipated in the past months, after some signs of improvement earlier in the year, and would continue to weigh on sales in the last months of 2022.

This was expected to have limited adjusted earnings before interest, taxes and amortisation (EBITA) to 210 million euros in the third quarter, down from 512 million euros a year before.

Philips also slashed its outlook for the fourth quarter, as it now expects a "mid-single-digit" comparable sales decline while it previously guided for improvement towards the end of the year.

"This weakness will also spill into 2023 where consensus on adjusted EBITA probably also needs to come down by at least 10%," ING analyst Marc Hesselink said in a note.

"Next step will be the 2025 targets which became very challenging especially now that the Sleep & Respiratory care business is not expected to fully recover post the recall."

RECALL HITS SLEEP BUSINESS

Philips last year shocked investors by recalling 5.5 million ventilators used to treat sleep apnoea, over worries that foam used in the machines could become toxic.

Outgoing Chief Executive Frans van Houten said the impairment on the sleep care business was the "best estimate" of the effects of a consent decree proposed by the U.S. Food and Drug Administration to solve the problems, which have lopped around 28 billion euros off Philips' market value in the past 15 months.

"Details of the consent decree have not been fully negotiated at this time," Van Houten said in a call with analysts. "It's really early days, we can't give much more detail today."

Van Houten will hand over the reins of the company to newly elected CEO Roy Jakobs by the end of the week, after Philips in August had unexpectedly announced his departure.

Philips will publish its full third-quarter results on Oct. 24.

https://money.usnews.com/investing/news/articles/2022-10-12/philips-says-q3-core-profit-to-drop-60-as-supply-chain-problems-persist

FDA authorizes updated COVID booster for children aged 5-11

 

The U.S. Food and Drug Administration on Wednesday authorized Omicron-tailored COVID-19 booster shots from Moderna Inc as well as Pfizer Inc and its partner BioNTech SE for children, a move that will boost the government's fall vaccination campaign.

https://www.marketscreener.com/news/latest/U-S-FDA-authorizes-updated-COVID-booster-for-children-aged-5-11--41991218/

Prame looks like the real deal

 When Roche launches a diagnostic for a novel cancer antigen the endorsement, in terms of target validation, counts for a lot. And this is precisely the endorsement that Prame, a target around which excitement had been building over the past year, got this morning.

True, the Roche assay is not intended to guide the type of pharmacological treatment, but rather to assess whether a tumour is malignant. But the development comes just a day after Immatics reported the biggest and most promising clinical dataset with a Prame-targeting therapy to date – a happy coincidence for the German cell therapy player.

The Immatics results came from phase 1 cohorts of a study of the anti-Prame engineered T-cell receptor IMA203, and represented an important update to a dataset that had piqued interest at last year’s SITC meeting. They were enough to send the group’s Nasdaq stock up 12% yesterday, and enable it to close a $110m secondary share offering.

Roche, meanwhile, today launched the Prame (EPR20330) Antibody, which runs on the company’s IHC/ISH instruments, and is intended for use specifically on tissue samples from patients with suspected melanoma. Roche says that, because Prame is expressed in most melanomas, the assay can be used to differentiate between benign and malignant lesions.

Focus on melanoma

A day earlier Immatics’ data pointed in a similar direction. Though Immatics cited Prame’s highly cancer-specific expression on many solid cancers, including lung and ovarian, its update suggested that IMA203’s best activity was in melanoma, including cutaneous and uveal subtypes. Prame is shorthand for "preferentially expressed antigen of melanoma".

A year ago the phase 1 trial in question had yielded eight remissions among 16 evaluable patients on the first three dose levels of IMA203; four quickly relapsed. Yesterday the result was updated for a fourth dose, and with that initial dose-escalation cohort now at 27 evaluable subjects the ORR at six weeks stood at 48%.

The bad news is that relapses here were still a problem: six weeks later the confirmed ORR was just 19%, or 29% among six subjects at dose level 4.

However, the good news came from a separate dose-expansion group using a new manufacturing process, in which three of four dose level 4 patients had confirmed remissions at week 12 – as did one patient treated with an even higher, exploratory dose.

Thus Immatics was able to make a headline claim that treating patients at dose level 4 or higher resulted in a confirmed ORR of 50%, or 80% if looking just at the second cohort, in which all responses were ongoing at the September 22 cut-off. Prame, it said, was now clinically validated as a multi-tumour target.

The other thing in Immatics’ favour, and which backs its claim that Prame is not expressed especially well in normal tissue, is safety. There are few off-tumour effects in its trial, and cytokine release and neurotoxicity appear at relatively low levels.

If this is the case one obvious question is why no one before Immatics has been able to seize on the potential of Prame, which has been studied by industry for some time. Immatics says ATR203 has improved affinity thanks to enhanced pairing of TCR chains, as well as high avidity and low off-target toxicity.

The group has not finished yet. The first patient was treated in August with an improved version of ATR203 coded IMA203CD8, and initial data are due next year. Competitors, including Immunocore, which disappointed at Esmo, and Biontech, which did a Prame deal with Medigene in February, will pay attention.

Selected projects targeting Prame
Company	Project	Modality	Clinical trial	Note
Immatics	IMA203	eTCR (HLA-A*02-specific)	NCT03686124	Oct 2022: 53% ORR, including 50% confirmed ORR at ph2 dose or above
Immatics	IMA203CD8	As above, but adds CD8 co-receptor to allow CD4+ T cells to be utilised		First patient treated Aug 2022; data 2023
Immunocore	IMC-F106C	Immtac (HLA-A*02:01-specific)	NCT04262466	Disappointed at Esmo 2022: 23% ORR, vs 38% cited in abstract
Medigene	MDG1011	eTCR (HLA-A*02:01-specific)	NCT03503968	Feb 2022: 1 short-term remission in 8 evaluable patients
Neximmune	NEXI-001	WT1, Prame & cyclin A1 vaccine	NCT04284228	Data due in Q4 2022
Mana Therapeutics	Mana-312	WT1, Prame & Survivin vaccine	NCT04679194	No news since 2021 series A
Bellicum	BPX-701	eTCR (HLA-A*02:01-specific; rimiducid-activated suicide switch)	NCT02743611	Deprioritised
GSK	GSK2302032A	Prame vaccine	NCT01853878	Discontinued
Mannkind	MKC1106-PP	Prame & PSMA vaccine	NCT00423254	Discontinued
Biontech/ Medigene	MDG1014	eTCR (PD-1/4-1BB switch receptor)	NA	Deal in Feb 2022
GSK/ Adaptimmune	Unnamed	eTCR	NA	$4m preclinical development milestone in 2021
Myrio (formerly Affinity Bio)	Unnamed	Bispecific T-cell engager	NA	Preclinical
Source: Evaluate Pharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/trial-results/prame-looks-real-deal

Walmart follows CVS, Walgreens into clinical trial sector

 Walmart is the latest US retail pharmacy giant to announce its intention of disrupting the clinical trials category, with the launch of a new institute that pledges to increase and diversify community access to healthcare research.

The Walmart Healthcare Research Institute (WHRI) won’t be running trials itself, but will spearhead Walmart’s efforts to connect patients who visit its massive, nationwide chain of health centres with organisations running clinical trials.

The move follows in the footsteps of both Walgreens and CVS, which have both launched clinical trial services businesses in the last year with the aim of matching patients with trial sponsors.

All three say their network of locations – which include socially vulnerable areas, will help to improve recruitment of under-represented groups, including African-American, Asian, Hispanic, and Latino people in clinical studies.

WHRI will be focused on therapies that can make a difference in populations including older adults, rural residents, women, and minority populations, said Walgreens in a statement, and will focus particularly on chronic healthcare conditions.

According to the FDA, in 2020 around three quarters of clinical trial participants in the US were white, while just 11% were Hispanic, 8% were Black, and 6% were Asian. Moreover, less than 4% of Americans participate in clinical trials, and around a third of those that do so drop out before the study is completed, with the loss of important data.

“We know our customers are interested in participating in healthcare research, but many have not had access until now,” said Dr John Wigneswaran, Walmart’s chief medical officer, adding that Walmart’s existing activities in this area are already achieving a threefold improvement in referrals compared to industry benchmarks.

He also pointed out that around 90% of Americans live within 10 miles of a Walmart outlet, giving it enormous reach across the country.

“We are already making an impact for our customers and for medical research, by raising patient trust and engagement in their care,” he continued, pointing to ongoing relationships with a wide range of study partners, including clinical research organisations, pharma companies, and academic medical centres.

Walmart is accompanying the formation of the WHRI with the launch of a digital tool called MyHealthJourney, which will help patients take control of their own data by providing some medical records and insurance information in one place.

The app will provide reminders for appointments and other healthcare services, and also serve as a conduit to enable participation in research studies.

https://pharmaphorum.com/news/walmart-follows-cvs-walgreens-into-clinical-trial-sector/

BriaCell in Phase 1/2 Study in Advanced Breast Cancer Patients

 BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX: BCT) (“BriaCell” or the “Company”), a clinical-stage biotechnology company specializing in targeted immunotherapies for cancer, announces today that it has added Mayo Clinic, Jacksonville, Florida as a clinical site in the Phase I/II study of BriaCell’s lead candidate, Bria-IMT™, with Incyte’s PD-1 inhibitor, retifanlimab, in advanced breast cancer.

“We are thrilled to be working with the clinical experts at Mayo Clinic and other top cancer centers across the United States. We believe that with our immunotherapy's novel mechanism of action, continuous innovations and improvements, and a Fast Track path to approval, we have great potential to improve patients’ lives,” stated Dr. Giuseppe Del Priore, BriaCell’s Chief Medical Officer.

https://www.biospace.com/article/releases/briacell-announces-new-clinical-trial-site-to-bring-novel-cancer-treatments-to-advanced-breast-cancer-patients/

Leap Starts Phase 2 Trial in Gastric Cancer

 Leap Therapeutics Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today announced that the first patient has been enrolled in the randomized controlled Part C of the ongoing DisTinGuish study to evaluate DKN-01, Leap's anti-Dickkopf-1 (DKK1) antibody, in combination with tislelizumab, BeiGene's anti-PD-1 antibody, and chemotherapy compared to a tislelizumab and chemotherapy control arm, in patients with gastric or gastroesophageal junction cancer (G/GEJ).

"We are excited to announce another important milestone for our DKN-01 clinical program in combination with our partner BeiGene's tislelizumab, advancing this unique combination therapy into Part C of the DisTinGuish study," said Cynthia Sirard M.D., Chief Medical Officer of Leap Therapeutics. "The data to date from the DisTinGuish study show the DKN-01 plus tislelizumab combination therapy to be a compelling potential treatment for patients with G/GEJ cancer with response rates and survival outcomes that exceeded the benchmarks. This first randomized controlled study for DKN-01 will characterize the treatment effect in first-line patients, with a particular emphasis on those in the aggressive DKK1-high population."

The DisTinGuish study (NCT04363801) is a Phase 2 study of DKN-01 in combination with tislelizumab and standard of care (SOC) chemotherapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. Part C of the DisTinGuish study will enroll approximately 160 first-line, HER2-negative patients. Patients will be randomized 1:1 to evaluate DKN-01 in combination with tislelizumab and standard of care (SOC) chemotherapy, compared to tislelizumab and SOC chemotherapy. The primary objective is progression-free survival (PFS) in DKK1-high patients. Secondary objectives of Part C include PFS in all patients regardless of DKK1 expression, as well as overall survival and objective response rate as measured by RECIST v1.1 in DKK1-high and all patients.

https://www.biospace.com/article/releases/leap-therapeutics-announces-first-patient-enrolled-in-part-c-of-phase-2-distinguish-study-of-dkn-01-in-combination-with-tislelizumab-for-the-treatment-of-gastric-or-gastroesophageal-junction-cancer/

Coherus, Junshi: Positive Results in Phase 3 cancer combo trial

 Toripalimab in combination with chemotherapy was associated with significant improvements in PFS and OS compared with chemotherapy alone in patients with advanced NSCLC without EGFR/ALK mutations, regardless of PD-L1 expression

– Supports combination development of toripalimab plus anti-TIGIT in NSCLC and other solid tumor indications

https://www.biospace.com/article/coherus-and-junshi-biosciences-announce-publication-of-positive-results-from-choice-01-a-phase-3-clinical-trial-evaluating-toripalimab/