Chronic Kidney Disease (CKD): Practice Essentials, Pathophysiology, Etiology

Endeavor Pulls In $132M To Back Cancer, Lung Disease Drugs

Endeavor BioMedicines has raised $132.5 million in a Series C round designed to advance its two experimental medicines deeper into clinical testing, the San Diego company announced Wednesday.

The round was led by AyurMaya, an affiliate of investment firm Matrix Capital Management. Originally, the company's financing target was between $75 million and $100 million, according to CEO John Hood. But Endeavor upped its expectations after reaching out to investors late last year.

Hood and his team found strong interest in a biotech with two drugs in early- and mid-stage testing, suggestive of the current investment climate favoring more mature drug startups. The company revealed positive Phase 2 study results in January while putting its funding together.

"We got the luxury of raising on really good clinical data for a disease with high unmet need," Hood told BioPharma Dive, in an interview.

With Endeavor, Hood is following a similar strategy as the last biotech he founded, Impact Biosciences. He formed that company around a myelofibrosis drug that was licensed from Sanofi. Impact's progress eventually drew the interest of Celgene, which acquired the company for $7 billion in 2018. The drug, Inrebic, was approved a year later and is now sold by Bristol Myers Squibb.

Endeavor, which launched in 2021, is also developing medicines that originated elsewhere. Its lead program, known as ENV-101, was first discovered by Eli Lilly and changed hands multiple times before arriving at Endeavor. Its second prospect, ENV-501, was licensed last year from Singapore-based startup Hummingbird Bioscience. (A third, that's no longer in development, was acquired from a pair of academic institutions.)

The two drugs have little in common: ENV-101 is being developed for idiopathic pulmonary fibrosis, while ENV-501 is a cancer medicine. But Hood views both as potential advances in the diseases they're targeting. "I'm not going to do this, and my investors aren't interested in doing this, just to have a 'me-too,' or an incremental drug," he said.

ENV-101, once known as taladegib, blocks a cellular pathway dubbed "hedgehog" that plays an important role in wound healing as well as tumor progression. As with other so-called hedgehog inhibitors, such as Roche's Erivedge and Novartis' Odomzo, it was initially developed for a type of skin cancer. But Endeavor has been exploring its use in idiopathic pulmonary fibrosis, a rare disease that causes scarring to build up in the lungs.

Preliminary Phase 2 study results suggested the drug may improve on standard therapies that can only slow the decline of lung function. The company will use the new funds to test that theory further. It's planning a Phase 2b study in IPF, as well as progressive pulmonary fibrosis, later this year.

ENV-501, meanwhile, is a type of targeted cancer medicine known as an antibody-drug conjugate, or ADC, which fuses an antibody to a tumor-killing toxin. Endeavor is testing it against cancers expressing the protein HER3.

ENV-501 trails more advanced HER3-targeting ADCs, most notably a therapy from Merck & Co. And Daiichi Sankyo that's under regulatory review. But it claims ENV-501 may be safer and more potent because of certain features, such as a particular "linker" molecule meant to more precisely deliver the drug to tumors, according to Hood.

Endeavor plans to start an early-stage trial in solid tumors this year.

Correction: A previous version of this story misidentified Daiichi Sankyo's partner on the HER3 ADC the company is developing.

Controlled-release Morphine May Reduce Cough Frequency In IPF

Low doses of controlled-release morphine, a natural opioid derived from the opium poppy, may reduce the frequency of daytime cough in people with idiopathic pulmonary fibrosis (IPF), according to data from a Phase 2 clinical trial.

In the trial, called PACIFY COUGH (NCT04429516), patients who were experiencing persistent cough for at least eight weeks (two months) also saw their quality of life improve after being treated with morphine, but not a placebo, suggesting that morphine may be an option for palliative care.

"There is no direct evidence to guide the treatment of cough in IPF," the researchers wrote. "The results of this trial are important for [the] almost 85% of patients with IPF who have cough and the clinicians involved in their treatment."

Findings were detailed in the study, "Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial," published in The Lancet Respiratory Medicine.

IPF is a lung disease of unknown cause in which lung tissues becomes scarred and stiff over time, making it hard for patients to breathe. People with IPF often experience a persistent cough that can be distressing and for which there are no proven treatments.

Like other opioids, morphine is thought to block the cough reflex — a mechanism that causes muscles in the chest and abdomen to push air out of the lungs to force out dust or other foreign particles. However, opioids can become addictive and have serious side effects.

"Although morphine is frequently used as a palliative agent for [shortness of breath] in IPF, its effect on cough has never been tested," the researchers wrote.

The study and its results

Here, a group of international researchers came together to test how safe low doses of controlled-release morphine are in people with IPF and how effective they are versus a placebo in reducing the frequency of daytime cough.

Controlled-release capsules do not release morphine continuously over the course of a dosing interval, which not only prolongs morphine's action, but also keeps its levels within the therapeutic window to avoid peaks that may lead to side effects.

The trial included 31 men and 13 women, mean age 71, with a recent diagnosis of IPF. All reported a persistent cough lasting more than eight weeks.

More than half (59%) were taking antifibrotics to slow down scarring. Nineteen (43%) had acid reflux, and 13 (30%) were using proton pump inhibitors to ease acid reflux.

Patients were randomly assigned to receive oral controlled-release capsules containing 5 mg of morphine or a placebo, twice daily, for 14 days (two weeks). After a seven-day break, those who had been initially assigned to morphine switched to a placebo, and vice versa.

Daytime cough was tracked using a recording device with a microphone and sensor worn on the chest. Periods of silence and noncough sounds were removed from the recorded files using special software, and the number of coughs was manually counted.

Controlled-release morphine reduced the frequency of daytime cough by 39.4% compared with a placebo. Over the 14 days of treatment with morphine, mean daytime cough frequency dropped by 40.8% — from 21.6 to 12.8 coughs per hours. With the placebo, there was a 4.3% drop, with the mean number of coughs per hour decreasing from 21.5 to 20.6.

Treatment with controlled-release morphine also improved all cough-related patient-reported outcomes.

A larger increase in the score of the Leicester Cough Questionnaire — a cough-specific quality-of-life score that ranges from 3 to 21, with higher values indicating a better quality of life — was seen after treatment with morphine compared with a placebo (1.8 vs. 0.6 points).

According to the Global Impression of Change, which reflects a patient's belief about the efficacy of treatment, controlled-release morphine eased symptoms of cough in 24 (56%) patients and improved overall quality of life in 14 (32%).

"The improvements in subjective and objective cough count and associated benefits in quality of life with morphine suggest that the drug offers an effective treatment option for this group of patients," the researchers wrote.

Patients adhered well to treatment with morphine, and the most common side effects of morphine were constipation (21%) and nausea (14%). One patient experienced moderate nausea and severe hypersomnia (excessive sleepiness) and discontinued treatment.

While short-term use of morphine improved cough by 20% or more in over half of the patients in the trial, "longer term studies should be conducted to establish the durability of its effects and the impact of improving cough on disease outcomes," the researchers wrote.

Endeavor Raises $132M In Oversubscribed Series C To Advance Lung Disease, ADC Candidates

Pictured: Photo illustration of hundred dollar bill and graph/iStock, Darren415

San Diego-based Endeavor BioMedicines has secured $132.5 million in an oversubscribed Series C round to advance its lead lung disease candidate and next-generation HER3-targeted antibody-drug conjugate, the biotech announced Wednesday. 

The financing will be used for ENV-101, a potential treatment for idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). Endeavor completed a Phase IIa trial for the candidate in January 2024 and plans to initiate a Phase IIb sometime later this year.

ENV-101's preliminary results have shown a potential to modify the disease and present treatment outcomes that "go beyond slowing disease progression" for those with IPF. The biotech plans to disclose the full results at a conference next month.

According to Endeavor, the drug goes after the underlying causes of fibrosis by inhibiting the cellular signaling pathway known as hedgehog, which aims to stop the accumulation of the myofibroblasts that can cause the disease. 

Endeavor is also moving forward with its anti-HER3 antibody-drug conjugate (ADC), dubbed ENV-501, targeting solid tumors and will start a Phase I/II trial later this year. The company acquired the exclusive worldwide rights to the ADC in October 2023 from Hummingbird Biosciences in a deal worth $430 million in upfront and milestone payments.

"Endeavor BioMedicines has the momentum, coupled with the right team and the necessary financing, to advance our mission of delivering transformational medicines to patients who need them," Endeavor CEO John Hood said in a statement. 

Matrix Capital Management affiliate AyurMaya led the oversubscribed round with new investors, Fidelity Management & Research Company, Velosity Capital, Woodline Partners, Invus and Symbiosis participating. Existing investors in the round included T. Rowe Price Associates, Ally Bridge Group, Avidity Partners, Eckuity Capital and Omega Funds, among others. 

"Endeavor BioMedicines' novel drug candidates have the potential to disrupt the underlying mechanisms that cause serious, life-threatening diseases," Karan Takhar, senior managing director at Matrix, said in a statement. "I look forward to collaborating with Endeavor BioMedicines' executive team and other members of the board to support the company's clinical execution as it pursues significant milestones in 2024 and beyond."

Endeavor emerged in early 2021 with a $62 million Series A and secured a $101 million Series B in February 2022. 

Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.Patchen@biospace.Com. Follow him on LinkedIn. 

---