Bio Man

Sharing some thoughts on $INO vs $PGEN: First, congrats to $INO longs. You took the risk and it paid off. Kudos to @AaronRosenblum5 on the fantastic write-up. Also, congrats to the #RRP community - more options for patients is always better, just listen to the lived experience of these patients… they absolutely deserve it. I’m also thrilled for the ENT providers that treat these patients. I interviewed a few of them in preparation for my initial investment in $PGEN. The empowerment that comes with offering patients something more than just surgery-after-surgery is big. Now, most of you in the name are likely in it for the quick flip - but for those who plan to follow the commercial story, keep reading. 1. Immunogenicity likely matters - especially for time to response. Folks are touting the milder AE profile of VOCERYQ and at surface level it looks great. Note, however, that VOCERYQ is formulated with IL-12 to enhance an immune response but despite this only 7 out of the 26 efficacy valuable patients had a complete response (27%) - defined as no requirement for surgical intervention in the 12 months after treatment. In PRGN-2012-201, 18 out of 35 patients treated with PAPZIMEOS had a complete response (51%). It’s also had a much higher rate of ISRs (most mild), fever, and chills. Raising the question - is it the vector, antigens, or both? In late 2024, $INO shared a retrospective analysis showing that the CR rate had increased to 50% (13 patients, up from 7) by end of year 2 and 54% by end of year 3. No update has been shared since. $PGEN has shared a 3-year and more recently, 4-year durability dataset. At most recent cut-off, 15 out of 18 complete responders continued to demonstrate ongoing responses at 36 months. 5 of these have ongoing responses greater than 4 years. Median duration of complete response has not been reached so look forward to the 5-year analysis. While both have shown impressive depth of responses by end of year 2, PAPZIMEOS had a much higher response rate by end of year 1. This, in conjunction with higher quality data, should be quite important to both patients and payors alike. Wouldn’t you want relief sooner? And if you’re a payor, wouldn’t you want reduction in surgical claims sooner? $INO bulls point out that VOCERYQ doesn’t require the extra procedure mid-treatment that PAPZIMEOS mandates if there are visible papillomas (to ensure minimal residual disease) however I’m curious as to whether this ended up working against VOCERYQ. How many of the late complete responders required a single surgery after VOCERYQ? Might be a good idea for $INO to revisit this. 2. The path forward for $INO’s confirmatory study is unclear. There are clear deficiencies with the data package that led to management applying for accelerated approval rather than full approval. Keep in mind, it was under @VPrasadMDMPH’s tenure that PAPZIMEOS was approved. VP had even highlighted that the approval highlighted the agencies regulatory flexibility when it came to single-arm studies in rare disease and of course the effect size with PAPZIMEOS likely drove this. I wonder what the confirmatory study will look like. I can’t imagine a placebo controlled study with PAPZIMEOS on the market. It’d have to be another single arm study with a larger sample size