ERG

FogPharma is renaming itself as Parabilis Medicines, announcing a new corporate identity Monday that reflects the imprint left by CEO Mathai Mammen since joining in 2023. The name change is the highest-profile sign of Mammen’s tenure, but the former Johnson & Johnson R&D head has also reshaped its workforce, its next cancer programs and the focus of its platform. In an exclusive interview with Endpoints News , Mammen said the rebrand acknowledges that the startup is “a very different-looking company than we were 16 months ago” when he started. Founded in 2016 by biotech entrepreneur Greg Verdine , Fog is an acronym for “Friends of Greg” referencing the high-net-worth individuals who backed its seed round. Part of the reason for the new name, Mammen said, is Fog couldn’t be trademarked and would sometimes get confused with similarly named Foghorn Therapeutics. Verdine left the board in June, after serving as vice chair for a year to help with the transition. The Cambridge, MA-based biotech is developing helix-shaped peptide drugs to slip inside cells with more binding power than small molecules. Its lead program, FOG-001, entered the clinic last June, and Mammen said they expect an initial data readout at a medical conference in the first half of 2025. FOG-001 targets beta-catenin, a hard-to-drug protein that drives many cancer cases, particularly in colorectal, prostate, and melanoma. An ongoing Phase 1/2 study is primarily enrolling late-stage colorectal cancer patients who don’t have other treatment options. Mammen called emerging clinical data “really encouraging,” as he expects to finish dose escalation in the coming months. “I’ve seen a lot of drug programs,” Mammen said, citing his J&J experience. “I feel like I have an eye for what might work, and this one feels very much like a drug to me.” Mammen said the company is considering potential pharma partnerships, particularly on FOG-001, which he called “a very complicated program” given the range of cancer types and potential combination therapies that could be tested. While FOG-001 was headed into the clinic before Mammen arrived, he has been hands-on in selecting Parabilis’ next programs. He’s prioritized its efforts in protein degradation, seeing its peptide approach as well-suited to tackling proteins that small-molecule degraders can’t hit. He highlighted four preclinical programs to watch beyond FOG-001, three of which are respectively degraders of beta-catenin, ERG, and AR. The fourth program is a radioligand therapy in collaboration with Artbio. Parabilis could soon be selecting development candidates for all of these programs, Mammen said, with the ERG degrader expected to reach that milestone in the next quarter or two. The broad goal is to begin filing INDs for these programs at the end of 2025 and into 2026, he added. “We’re really excited about these four as diversifying well beyond ‘001,” he said. With its $145 million Series E round announced earlier this year , Parabilis has a cash runway into 2026, Mammen said. The company has raised just over $500 million since its founding.

Researchers have shown that targeting a gene regulated by two cancer-fuelling proteins can kill cancerous cells and halt their growth in laboratory models of B-cell acute lymphoblastic leukemia (ALL). Researchers have found a new way to potentially treat one of the most common forms of acute lymphoblastic leukaemia. The study, led by WEHI and the Peter MacCallum Cancer Centre, was able to kill leukaemia cells in the lab and stop cancer cells from growing, after identifying two new proteins critical for the development of the aggressive disease. The findings could lead to enhanced treatment options in the future, with plans underway to develop a clinical trial based on the research. Around 5200 people are diagnosed with a form of leukaemia in Australia each year. An estimated 1500 of these cases are acute -- meaning the blood cancer appears suddenly and grows quickly. Blood cancers like leukaemia are notoriously difficult to treat in adults, with 50% of Australian patients relapsing after the first round of chemotherapy and subsequently becoming resistant to further treatments. Associate Professor Ashley Ng, a corresponding author on the paper, said this presented a unique treatment challenge for these blood cancers and highlighted the urgent need for new therapeutics. "About 135,000 people live with a blood cancer or blood disorder in Australia, with 16 people dying every day from the disease," Assoc Prof Ng, a WEHI researcher and clinical haematologist at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, said. "Despite the medical advancements made in the cancer field over the years, the incidence of blood cancer has grown by 47% in the past decade. "The best way to enhance treatment options for patients is to continually improve our understanding of how leukaemia cancers behave and what drives their growth. "Our new research has identified two proteins that are critical for the development of B-cell acute lymphoblastic leukaemia, expanding our knowledge into how these cancers can form. "By uncovering this new vulnerability in leukaemia formation, we hope to exploit the findings for therapeutic benefit and also apply them to other forms of the disease." The research is published in the journal Science Advances. Master regulators Assoc Prof Ng has spent over a decade researching a protein that regulates gene activity in the cell nucleus, known as ERG. Imbalances in this protein can lead to blood cancers, like acute lymphoblastic leukaemia. His previous research uncovered the protein's critical role in Down syndrome associated blood disease and normal blood cell function, including how B cells -- which are essential for producing antibodies to fight against infections -- develop. First author Dr Kira Behrens said the research team wanted to understand what other types of proteins ERG works with to fuel leukaemia development. "We looked at the proteins that control how specific genes switch 'on' or 'off' to analyse how normal B-cells -- and critically -- B-cell acute lymphoblastic leukaemia -- can develop," Dr Behrens said. "After analysing the genes regulated by ERG and another protein, c-MYC, we discovered that these proteins were actually the master regulators of several important pathways and processes within the leukaemia cell." Researchers then narrowed the list down to focus on one pathway essential for making proteins, known as ribosome biogenesis. This led the team to focus on targeting a key gene essential to this pathway, POL I, which is also controlled by these master regulator proteins. The gene helps direct an important cell growth and division process that can lead to the development of cancer if it goes awry. Dr Behrens said: "By targeting POL I with inhibitors, we were able to kill leukaemia cells and stop their growth in our pre-clinical and human tissue models." "This was a surprising, yet remarkable discovery, as we were able to unravel a new pathway and potential drug target that can hopefully be used in the fight against leukaemia in the future." The study also involved a collaboration with Associate Professor Elaine Sanij (St. Vincent's Institute of Medical Research) whose work focuses on targeting POL I and ribosome biogenesis in cancer therapy. "The findings show that a subset of aggressive acute lymphoblastic leukaemia exhibit a form of addiction to producing of ribosomes, the protein making molecular machinery," Assoc Prof Sanij said. "They render this aggressive leukaemia sensitive to POL I inhibitors which target ribosome production. "Altogether, our work highlights the importance of developing this new approach to cancer therapy to treat oncogene-driven cancers." Collaborative power One of the drugs used in the study to target POL I was an agent developed by the Peter MacCallum Cancer Centre. Professor Rick Pearson, former Associate Director of Laboratory Research at Peter Mac, said the team hopes to mimic the study in a future clinical trial to help patients with acute lymphoblastic leukaemia. "We worked with WEHI researchers to confirm our agent is effective in targeting POL I activity and demonstrated its potency in impeding the leukaemia cell growth and division. "These findings highlight the power of collaboration and the remarkable results that can be achieved when bringing together experts from across various areas. "We hope this research will translate into successful clinical trials and potentially offer doctors a new treatment option for patients with acute lymphoblastic leukaemia," Professor Pearson said. This research was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft), the National Health and Medical Research Council (NHMRC), Cancer Council Victoria, National Stem Cell Foundation of Australia, the Leukaemia Foundation and Victorian Cancer Agency. The study, "ERG and c-MYC Regulate a Critical Gene Network in BCR::ABL1-Driven B-cell Acute Lymphoblastic Leukaemia," is published in Science Advances.

FogPharma took the amount raised from investors since its inception nearly a decade ago to more than $500 million after closing another round of financing. The latest Series E fundraising – led by Nextech Invest - brought in $145 million and featured a host of new investors, including former Johnson & Johnson CEO Alex Gorsky.The company added that in conjunction with the financing, Nextech’s nominee Alexis Borisy joined the board. Mathai Mammen, FogPharma’s CEO said the investment, which follows a period of rapid growth for the drugmaker, will allow it “to execute on our expanded clinical development and commercialisation strategy” for its lead asset, the intracellular TCF-blocking β-catenin inhibitor FOG-001.“Millions of colorectal cancer patients have been told by their oncologists that no more can be done for them,” Mammen remarked, adding “we believe FOG-001 may represent the long-awaited major technological breakthrough needed to address one of the most common yet unaddressed oncogenic signalling pathways.” Mammen joined FogPharma last year having stepped down from his role as head of pharmaceuticals R&D at Johnson & Johnson in 2022.The company is using its Helicon peptide platform against biologically validated disease-driving intracellular targets that have never before been drugged. FOG-001 is designed to block the key oncogenic step in the Wnt/β-catenin signalling pathway with the first patient dosed last year in a Phase I/II study in solid tumours. FogPharma said that the funding will also support its other discovery efforts, which include programmes targeting ERG, CCNE1 and RAS.FogPharma raised $178 million via a Series D financing in 2022, adding to $107 million pulled in from a Series C round a year earlier and a $66-million Series B fundraising in 2018.