Bill W. writes, "Hi, Adam, your sharp reporting got me safely out of Cel Sci (CVM), and I wish I had listened to you on that piece of $%^@ Generex (GNBT). Now, I would really appreciate your view on ImmunoCellular Therapeutics (IMUC), which had a nice pop. Is ImmunoCellular of the same shyster ilk as those other two?" No, ImmunoCellular is not as stinky as Cel-Sci or Generex, but that doesn't make me a fan, either. The relevant question to ask about ImmunoCellular is this: Are you a trader or an investor? If you're the former, then by all means pay attention to ImmunoCellular and its brain tumor vaccine ICT-107 because every three to six months, the company seems to be promoted heavily to retail investors as the next great cancer vaccine stock. Naturally, these promotional efforts lift the stock price. Sometimes, ImmunoCellular takes advantage by raising money, sometimes it doesn't. Once the buzz fades -- and it always does -- ImmunoCellular's stock price falls.
PKR19 writes, "What do you make of Celldex Therapeutics (CLDX) raising money before telling us about its FDA meeting? It seems positive to me. They'd be crazy to do this and then tell us that FDA won't let them go for the accelerated approval. What do you think?" Positive, I agree. It's also bit odd for Celldex to tease us with hints about the next steps in the clinical development of CDX-011 in advanced breast cancer, but my educated guess is the company is waiting for the minutes from the FDA meeting and sign-off on the pivotal trial design before full disclosure. This is what Celldex said about CDX-011 in the prospectus filed with the SEC on Feb. 4: In December 2012, we had our end of Phase 2b meeting with the FDA for our CDX-011 program, which we have characterized as positive. Based on this meeting, we intend to initiate a CDX-011 study suitable for accelerated approval in the second half of 2013. We are currently finalizing the clinical trial design and will update investors on our plans for the accelerated approval trial on our year-end 2012 call in early March 2013. A CDX-011 pivotal study "suitable for accelerated approval" means a primary endpoint of overall response rate (ORR) or progression-free survival (PFS) and not overall survival. That's important because an ORR or PFS trial can be completed faster. Again, my guess is FDA will ask for a PFS primary endpoint. Response rate and overall survival will be key secondary endpoints. I'm also going to assume FDA wants Celldex to include a control arm in the CDX-011 pivotal study. The control arm will likely be offered treatment with doctor's best choice of alternative therapies, or perhaps best supportive care. Celldex has already said it wants the pivotal study to enroll women with heavily pre-treated, triple-negative breast cancer over-expressing the GPNMB protein that serves as the honing target for CDX-011.
BuggyFunBunny writes, "And what of nucs now that Idenix Pharmaceuticals (IDIX) abandons. Is the entire family done for?" Not all nucleoside/nucleotide polymerase inhibitors -- "nucs" -- in hepatitis C are the same. The chemical structure of these drugs matter. Guanosine-based nucs are bad. Bristol-Myers Squibb's ( BMY) BMS-096084 was a guanosine nuc and it caused severe cardiac toxicity, killing one patient in a clinical trial. Idenix didn't find cardiac toxicity with its guanosine nucs IDX184 and IDX19368, but FDA decided, smartly, that the safety risk of any guanosine-based nuc is too great. Gilead Sciences' ( GILD) blockbuster-in-the-making, sofosbuvir, is a uridine-based nuc, so is Vertex Pharmaceuticals' ( VRTX) VX-135. Idenix also has a uridine nuc in preclinical development, expected to begin human studies this year. Here's the simple rule: Uridine nuc good; guanosine nuc bad. Of course, not all uridine nucs are equally good, but that's a discussion for another day.
On a related note, @VendettaUhave asks, "$MDGN if the goal is to eliminate interferon therapy, is it pointless to invest here? Any upside in this name?" This is Medgenics ( MDGN): Doctors take some dermal tissue from just under the skin of the arm. This tissue sample is then placed inside a black box where the cells of the sample are genetically altered and programmed to produce a therapeutic protein (a drug) of your choice. The tissue sample -- now called a "biopump" -- is implanted back into the patient where it merrily produces drug. Multiple biopumps will be necessary. Really? Let's be overly generous and assume these Medgenics biopumps are actually capable of producing drugs at therapeutic levels. How do the biopumps know how much drug to deliver? How are appropriate blood levels of the drug maintained without a feedback loop or any way to turn them on or off? Do the biopumps work forever or do they wear out? What happens when they wear out? Are they removed? Do they need to be replaced? Medgenics is developing a biopump to produce the anemia-boosting drug EPO. Does this process really sound better or more convenient than simply giving a patient an injection of EPO when needed? The answer: no. The company is also developing a biopump to produce interferon as a treatment for hepatitis C. Well, by next year, hepatitis C patients won't require interferon. The next generation of potent direct antivirals coming soon from Gilead and others will make interferon injections obsolete. Hepatitis C patients will take a pill or two for 12 weeks and their hepatitis C infection will be cured. Isn't that a lot easier than having biopumps installed under your skin? Again, the answer is yes. Sol Barer, the former CEO of Celgene, is the chairman of Medgenics. Which prompts me to ask: "Sol, what the hell are you thinking?" -- Reported by Adam Feuerstein in Boston. Follow @AdamFeuerstein