Upcoming events – Biolinerx takes on pancreatic cancer and first data for Homology

Biolinerx’s BL-8040 needs to show improved responses in pancreatic cancer while investors will get a first look at Homology's HMI-102, a gene therapy for phenylketonuria.

Welcome to your weekly roundup of approaching clinical readouts. Pancreatic cancer has been marred by clinical setbacks, the most recent of which was the failure of Halozyme’s PEGPH20, and many hope that immuno-oncology might start to offer a way forward.

Up steps Biolinerx, the tiny Israeli biotech whose CXCR4 antagonist BL-8040 is being combined with Merck & Co’s Keytruda and chemotherapy in the phase II Combat/Keynote-202 trial in second-line patients. Data are due next month.

Response rates will be revealed at the Esmo-IO conference on December 13 and abstracts, due on December 5, will topline the data. More important survival results should emerge in the middle of next year.

The company hopes to show that adding chemotherapy can improve the response rates generated by the dual combination of BL-8040 and Keytruda that was tested in an earlier arm of the study. That generated a disease control rate – which counts responses and instances of stable disease – of 34.5% in 29 patients. The only response seen, however, was partial, though many patients had been heavily pretreated, with up to five lines of prior therapy. 

Median overall survival of 3.3 months in all patients improved to 7.5 months in the 17 patients that were considered second line. This finding prompted the triple combo arm to be restricted to a second-line population, though the small numbers involved here, and absence of any control, makes the next set of data hard to call. 

The only regimen to win approval in a second-line pancreatic cancer setting is Onivyde, 5-FU and leucovorin, on the basis of 6.1 months of overall survival versus 4.2 months for 5-FU/LV alone, which provides a yardstick of sorts. And while survival data are still some months off for Biolinerx, a big improvement in response rates over the dual therapy arm would lift hopes for the triple combo. 

FIXXing PKU

Homology, meanwhile, hopes that its gene therapy can offer a new approach to the enzyme deficiency disease phenylketonuria (PKU), a condition in which sufferers are unable to break down phenylalanine. The first clinical data on HMI-102, which transfects patients with a functional copy of the phenylalanine hydroxylase gene, are due before the end of the year.

Results from up to three adult patients will be reported from the phase I/II pheNIX study; initial data are expected from patients dosed with the lowest level to be tested, thought to be around 1-3 x 1013vg/kg. In total 21 subjects will be recruited.

The primary measure, alongside safety, is to drive phenylalanine levels under 360μmol/l; patients enrolled in the study start with levels of more than 600μmol/l. Analysts expect the lowest dose to show reductions in phenylalanine but reckon higher volumes of the gene therapy will be required to reach the desired efficacy.

Any sign of an immune response will be monitored closely as HMI-102 uses an AAV vector. To mitigate any increase in liver enzymes, which has been seen with other AAV-based gene therapies, subjects in the pheNIX trial are prophylactically dosed with steroids.

The data will provide the first look at Homology’s technology since the group completed its $166m IPO in March, and could position the company as the biggest threat to Biomarin in this disease area. Homology's shares are off 13% since the float.

Biomarin dominates PKU, with two products on the market including its enzyme-replacement therapy Palynziq. Its gene therapy project BMN 307 is due to start clinical testing next year.

Meanwhile, enthusiasm for Rubius’s RTX-134, which uses red blood cells to deliver the missing therapeutic protein, has taken a knock owing to delays over patient recruitment.  

Top five phenylketonuria treatments
Product Mechanism of action Company Sales ($m) 2024e Status Note
Palynziq PAL replacement Biomarin 563 Marketed Once-daily SC, black box warning for anaphylaxis
mRNA-3283 PAH mRNA therapeutic Moderna 400 Preclinical IND filing expected 2020
Kuvan Tetrahydrobiopterin (BH4) inhibitor Biomarin 171 Marketed Must be accompanied by a strict low-protein diet 
HMI-102 PAH gene transference Homology Medicines 139 Phase II pheNIX data due YE NCT03952156
RTX-134 PAL cell therapy Rubius Therapeutics 138* Phase I Company update at Jefferies conference noted that no patients had been dosed, but still guided to data due Q1 NCT04110496
*Forecasts before disclosure of delay. PAL=phenylalanine ammonia lyase, PAH=phenylalanine hydroxylase. Source: EvaluatePharma.

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