Base to Base Biotech

Times:03:22 Ona Therapeutics24:08 Actuate TherapeuticsThis week, we have a conversation with Valerie Vanhooren, CEO and co-founder of Ona Therapeutics about first-in-class ADCs for tackling tumours, and Daniel Schmitt, president and CEO of Actuate Therapeutics, about targeting multiple molecular pathways in cancer that are involved in promoting tumour growth.Ona TherapeuticsOna Therapeutics has reached an important milestone in its development, advancing as a clinical-stage company with its lead first-in-class ADC, ONA-255, now progressing through phase 1a clinical development. More than half of the planned patients have already been enrolled in the study.Alongside this, Ona has appointed oncologist and physician Aleix Prat as chief medical officer. Prat has worked closely with the company and played a key role in the identification and validation of the target underlying ONA-255.ONA-255 is a first-in-class ADC designed to target treatment-resistant tumour biology through a novel mechanism, with an initial focus on HR+/HER2-negative advanced breast cancer and gastric cancer. The programme represents an important milestone for Ona following its $86.6m series B financing earlier this year.The company continues to expand its ADC pipeline, with ONA-389 expected to enter the clinic in the second half of 2027ONA-418 is advancing a dual-linker, dual-payload approach designed to broaden the potential of Ona's ADC portfolio.Actuate TherapeuticsActuate Therapeutics is developing elraglusib, an investigational GSK-3β inhibitor that targets several pathways involved in tumour growth and drug resistance while also modulating anti-tumour immunity.In metastatic pancreatic cancer, randomised phase 2 results published in Nature Medicine showed that adding elraglusib to standard chemotherapy reduced the risk of death by 38% and roughly doubled 12-month survival. Since then, Actuate has secured FDA clearance for a phase 1/2 study of an oral tablet formulation and is working with both the FDA and EMA on a potential registrational study.The company recently shared new preclinical data from its work with the Mayo Clinic and Northwestern University showing synergy with Revolution Medicines' RAS inhibitors zoldonrasib and daraxonrasib, including in chemotherapy-resistant models.Elraglusib has also produced complete responses in a phase 1 trial in relapsed/refractory Ewing sarcoma, a paediatric cancer with no approved targeted therapies.To get in touch with guest suggestions, or to sponsor or advertise on the podcast, please email [email protected]

This week, we have a conversation with Philip Brainin, CEO of Isomab, about restoring blood flow to the heart, and with RougeTx CEO Andrew Lightfoot, about developing a treatment for hereditary haemorrhagic telangiectasia (HHT).Times:03:34 Isomab25:29 RougeTxIsomabIsomab, a preclinical UK biotech, recently presented safety data at ESC recently that may not sound particularly exciting at first glance, but the implications for cardiovascular drug development could be significant.For decades, the field has been trying to stimulate new blood vessel growth to restore blood flow to the heart, but concerns that this could increase the risk of cancer or damage to the retina have been a major barrier.Isomab’s systematic review of more than 20 years of clinical trial data found no evidence of these long-held safety concerns, potentially removing a significant obstacle to developing an entirely new class of disease-modifying cardiovascular therapies.Isomab believes its approach could open up a new avenue for treating coronary artery disease. The company has a lead drug candidate in ISM-001, which selectively removes VEGF-A165b to restore the natural signalling balance that enables healthy vascularisation in the heart. VEGF-A165b was first identified in 2001 by David Bates, scientific founder of Isomab, and has since been validated in more than 100 publications from more than 80 independent laboratories worldwide.RougeTxRougeTx, launched recently with a $58m Series A financing to advance first-in-class therapies designed to restore vascular integrity by targeting pericyte dysfunction.RougeTx is developing novel therapies for diseases driven by vascular instability, with lead programme RTX-001 advancing towards first-in-human clinical development for hereditary haemorrhagic telangiectasia (HHT), a serious inherited bleeding disorder for which there are currently no approved therapies.RougeTx's periSCOPE platform is being used to identify additional opportunities across diseases associated with vascular instability. The company is built on more than two decades of research into the role of pericytes in maintaining blood vessel integrity.To get in touch with guest suggestions, or to sponsor or advertise on the podcast, please email [email protected]

This week, we talk about mitochondria and obesity with Jon Rees, co-founder and CEO of MitoRx Therapeutics, and also have a chat with Apeximmune Therapeutics’ CEO and founder Li-Fen Lee, and senior director of biology Kan Lu, about a new breakthrough in shrinking tumours.Times:03:11 MitoRx Therapeutics25:06 Apeximmune TherapeuticsMitoRx TherapeuticsMitoRx Therapeutics is developing new treatments to restore healthy mitochondrial metabolism in patients living with high-risk obesity. Its first-in-class small molecule asset, MTRX31, targets the elimination of ectopic fat in people with metabolically unhealthy obesity, by restoring mitochondrial health rather than suppressing appetite.Preclinical data for MTRX31 has shown superior magnitude, quality and durability of weight loss compared with tirzepatide in an industry-standard preclinical model of obesity. MTRX31-driven weight loss does not involve lean mass loss, meaning basal metabolic rate is maintained – providing durable, healthy weight loss.The company recently presented new preclinical data at the EASD conference recently..Apeximmune TherapeuticsApeximmune Therapeutics, Inc. is an IND-stage biotechnology company in South San Francisco focused on developing novel immunotherapies for patients who do not respond to existing immune checkpoint inhibitors.The company applies proprietary computational target discovery to identify mechanistically distinct immune checkpoints with the potential to expand the reach of immuno-oncology. The company recently saw its research published in Nature with a piece entitled “PLA2G2D in tumour-draining lymph nodes regulates anti-tumour immunity.”The publication validated PLA2G2D as a novel and mechanistically distinct immune checkpoint capable of addressing resistance to anti-PD-1 therapy. The publication represents the convergence of two independent research programmes – one led by Apeximmune, the other by researchers at Erasmus University Medical Center in Rotterdam, the Netherlands – that arrived at the same target using different approaches. To get in touch with guest suggestions, or to sponsor or advertise on the podcast, please email [email protected]

This week, we chat with Ryan Beal, a cancer survivor and founder and CEO of Dyve Biosciences, about tumour acidity, and Gene Mack, president and CEO of Gain Therapeutics, about developing allosteric therapies, including taking Parkinson’s disease treatments beyond addressing symptoms.Times:03:03 Gain Therapeutics25:48 Dyve BiosciencesGain TherapeuticsGain Therapeutics is developing next-generation allosteric therapies. Its lead drug candidate, rexaceract is currently being evaluated for the treatment of Parkinson’s disease with or without a GBA1 mutation in a phase 1b clinical trial.Rexaceract has further potential in Gaucher’s disease, dementia with Lewy bodies, and Alzheimer’s disease. Also, it has multiple undisclosed preclinical assets targeting lysosomal storage disorders, metabolic diseases, and solid tumours.Its approach enables the discovery of novel, allosteric small molecule modulators that can restore or disrupt protein function. Deploying its Magellan platform, Gain is accelerating drug discovery and unlocking novel disease-modifying treatments for untreatable or difficult-to-treat disorders including neurodegenerative diseases, rare genetic disorders and oncology.Dyve BiosciencesRyan Beal, a cancer survivor and founder and CEO of Dyve Biosciences, invented a first-of-its-kind therapy that delivers sodium bicarbonate through the skin to target tumour acidity throughout the body. The therapy is designed to address a key limitation of earlier efforts, which relied on delivering large amounts of buffering agents orally.In preclinical research with Moffitt Cancer Center, DYV800 made tumours substantially less acidic, restored T-cell activity, slowed tumour growth and improved survival. The findings were recently published in Frontiers in Immunology, and the next step is bringing the therapy to patients.To get in touch with guest suggestions, or to sponsor or advertise on the podcast, please email [email protected]

This week, we chat with Simon Mølgaard, co-founder and chief executive officer of Teitur Trophics about results from its Parkinson’s disease trial, and have a conversation with Jordi Fàbrega, co-founder and CEO of CONNECTA Therapeutics, and Josep Prous, co-founder and chief scientific officer, about Fragile X syndrome.Times:03:15 Teitur Trophics14:03 CONNECTA TherapeuticsTeitur TrophicsTeitur Trophics recently announced successful results from its phase I clinical trial of its lead asset TT-P34 in healthy volunteers and patients with early-stage Parkinson’s disease (PD).The positive results support plans to initiate a phase II trial in PD patients in 2027, which will be designed to explore the therapeutic benefit and disease modifying potential of TT-P34.TT-P34 is a first-in-class therapy that, through a dual mechanism of action, improves both mitochondrial and lysosomal function. Its unique mode of action, targeting a critical pathway that underpins multiple aspects of pathology, means TT-P34 also has potential as a disease-modifying drug for other neurodegenerative conditions including frontotemporal dementia and Huntington’s disease.CONNECTACONNECTA Therapeutics is a Barcelona-based clinical-stage biotech company developing first-in-class neuroplasticity modulators for central nervous system (CNS) disorders.The company recently announced a €3.1m financing to support the advancement of CTH120, CONNECTA's lead programme for Fragile X syndrome (FXS), including completion of the ongoing phase IIa clinical trial in adult males with FXS, with topline data expected in mid-2027.The financing comes at a key stage for the company as it works to address the underlying neurobiology of FXS, a rare and currently untreatable neurodevelopmental disorder, through its differentiated neuroplasticity modulation platform.To get in touch with guest suggestions, or to sponsor or advertise on the podcast, please email [email protected]