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Mutations that have yielded a CR with TUSP: FLT3; IDH2; SRSF2; TP53; NPM1; DNMT3a; RUNX1; NRAS; SF3B1; RB1; MLL-PTD; BCOR; U2AF1; SETBP1
Mutations that have yielded a PR with TUSP: KRAS; IDH1; PTPN11; ASXL1; CBL
Preclinical Cell line data suggests the LUX is effective against mutant NRAS; IDH1; SRF2 and ASXL1.
Preclinical Cell line data suggests the LUX is effective against several mutants that are also hit by TUSP leading to potential additive or synergistic effects.
Both TUSP and LUX have very favorable safety profiles and both are synergistically enhanced by venetoclax. They have been combined in vitro (data not shown-yet).
Primary emergent resistance mutants to Gilteritinib are NRAS; KRAS; TP53.
I just listened to the Dec 11 APTO presentation again with focus on the monotherapy approval strategy. It appears that the decision to take AML r/r patients to HSCT will be left to the treating physicians. APTO believes that it should get credit for any CR patients that go to HSCT and will discuss this with the FDA. Everyone understands that many of the CR patients will not be treated with TUSP for six months before they get an HSCT. APTO also plans to petition the FDA to allow patients that get a HSCT to go back on TUSP in a maintenance setting. So I do not believe that the response duration is a straightforward DoR. It will likely be a hybrid of the above and agreed to with the FDA. N. Daver suggested that a CRc in the range of 20% should be viable for potential AA.
Good to see you respond. Yes I am the latest victim of woke on Yahoo. What's curious is that I posted a purely neutral response to a question and it got flagged. Oh well, perhaps we can create a new community here.
Regarding the latest presentation. I agree that the data provided does not currently support the planned targets for prior Flt3mut drug failures. That said I want to see some expansion data in that area. I am much more interested in the NPM1 results in Tusp monotherapy and the combinations data that they are just beginning to develop.
Regarding the 6 months. Many of the CRs are likely to go to HSCT long before that. Perhaps Rice will lobby for credit in that area.
I think that is why they are running the expansion phase with Flt3mut, prior inhibitor failures. They may also have a bit more up to date data than what we see.
Hello decaf7. Let me know if you see this message. I think I have also been blocked by Yahoo. Perhaps we can share here.
There is a lot happening in the DLBCL space. I can bring info over time, but it's not all SPPI stuff. I own several stocks with drugs active in DLBCL.
There's no need to rush anything. Salaries guaranteed for next several years.
I'm a bit less understanding at this point. SPPI watched the generics go through similar problems, but could not anticipate any CMC issues. That suggests some weakness in the management. Coupled with the BTD denial, you have to concede that they don't have their act together.
Still believe Rolontis and Poziexon20 will get approved, but expect a very bumpy road. After the MDACC presentation at EOM, I see no PPS moving news until 4th quarter.
Of course the PPS has and can move on no news. That's happened many times before. We just can't count on that. SPPI has a $1B market cap right now, so I think they need to advance the pipeline in a meaningful way to sustain any meaningful increase in PPS.
I think I'm being realistic here.
The reason the PPS did not tank is likely because most knew or suspected it was a CMC issue. That said SPPI had seven years to get those issues worked out.
I'll be happy with revenue over $300M. This set-back likely cost SPPI two quarters of income, so it's not trivial.
In any event we may see a gradual rise in PPS as we move through the spring and summer in anticipation of the news flow in forth quarter.
I just hope they are correct when they tell us that Pozi cohort 1 is registrational and that the data is on track for approval. Their credibility is shaky right now. It makes the risk/reward ratio more negative that necessary.
Do you know what this transfer is about? Are the moving manufacturing to the US? I have not paid much attention to this topic. TIA.
One of my problems is that SPPI never shows any sense of urgency. They have plenty of $$ now, probably expect Rolontis to deliver nice cash flow. So, I don't see anything lighting a fire under their butts.
Will be fun to see who is closer. Obviously I hope you are.
You are probably right. Let me say it another way. The only piece of news that I see that could pop the PPS before 4th quarter is MDACC presentation. How likely that is, I have no idea.
Therefore SPPI may be stuck in current range until 4th quarter.
Not saying there will be. Just saying I would not be surprised with a pop. Yes the data is in the abstract, but SPPI may do a meeting and the information may be more broadly advertised. Just something to watch. If nothing happens, I think PPS will meander until 4th Q.
Thanks for such an extensive response.
In thinking about the current market cap, I believe that uncertainty and time are the major factors keeping it down. We don't know what the Rolontis market will be and the roll-out of Poziexon20 data is going to stretch out over many years. Best case we get cohort 1, 2L+ EGFRexon20 approved in the US some time in 2021. I don't think they will file until mid-next year. Then we will see a steady stream of follow-on filings. Only Rolontis has any chance of providing a revenue stream until late 2021.
I see the valuation of SPPI rising relatively slowly but steadily over the next four to five years based on current drivers.
Of course we could get a BO at any time, if the Poziexon20 data is compelling. Odds of a BO will be significantly higher next year.
I think the PPS will likely be between the current $10 and $20 in 2019 but near that higher range only if SPPI delivers a driver. I'm wondering if the MDACC Pozi + T-DM1 data at end of month will drive PPS up to mid-range-i.e. $15. We'll see.
I've been wondering about SPPI's market cap. Is it correct at approximately $1B?
We have high probability of Rolontis approval. I'd say 80%, just because I have a bit less confidence in SPPI's management after the BTD. The revenue numbers for Rolontis are all over the place. I see a range from $50 to $250M for 2020. No idea what peak sale might be. If we take the average at 150 x 6 = 900M x .8 =720M corrected for time I think 500M is fair.
Pozi has many hurdles and uncertainties between now and first approval, so I think it should add about $300M to the market cap until we see the first cohort read-out. We don't know if SPPI can file for BLA based on cohort 1 data even though that is what they are saying. If that read-out is strong and they file, I would double the number to $600M.
Selling the existing product line reduces MC IMO. I give no value to the cash. SPPI will burn through that.
So, I think SPPI should be valued at about $800M right now subject to big adjustment in 4th quarter when PDUFA decision is made and we get cohort 1 data.
Excellent background work Antihama. I'm looking forward to the Pozi + T-DM1 data presentation by MDACC at the end of the month. I actually think it could lead to a pop in PPS. Not sure it will hold as combination clinical data is at least a couple years away.
As long as Poziotinib remains the best in class TKR candidate we are golden. But it's going to be a slow process and roll out of full value. Unless we get a buy out.
We know that KK and JT know each other very well. I thought it was KK who brought JT to SPPI. Could be interesting. But I don't see a synergy. Looks more like competition.
I sent an email to SESN asking their BD people to check out Qapzola. I own some SESN now, so I'd love to save Qapzola.
Don't get me started. Qapzola was the most miss-managed drug SPPI ever had, bar none. It was the winner we never got.
I recently purchase some shares of SESN just to own some Vicinium potential. I would love to see SESN buy Qapzola for pennies.
The problem is SPPI is going to make us wait until 4th quarter for any cohort 1 data. We may see a pop when MDACC reports on Pozi + T-DM1 at end of month, but it may not sustain with a news drought pending over the summer.
Wow. Unbelievable. Will need tall boots to wade through that.
Take a look at REPL yahoo board. James and I are the only major posters there. REPL is only six months old. Take the time to study the website. I really think you have the intelligence to grasp what ground floor opportunity this is. I've looked at a lot of small oncology companies over the last 9 months and REPL is among the most exciting ones I've found.
Since you are already focused on innate immunity to active immunity drugs, this should be an easy study for you.
If you like NWBO, I think you will love REPL.
Do you have an NWBO board on IHUB?
" The company plans to discuss the results with the U.S. Food and Drug Administration (FDA) regarding a potential new drug application (NDA) filing for accelerated approval. Umbralisib was recently granted Breakthrough Therapy Designation (BTD) by the FDA for the treatment of adult patients with MZL who have received at least one prior anti-CD20 regimen."
So it looks like they are not concerned about upsetting the FDA.
Maybe SPPI is just much more conservative or maybe SPPI doesn't want to share that data before getting a PDUFA decision for Rolontis. Just suspicious.
Don't know if you are interested but I am really excited about a new company called Replimune. Very exciting!
Actually I agree. I'm focused more on solid tumors also.
My point was that TGTX was willing to announce interim ORR data, whereas SPPI is making us wait until 4th quarter. SPPI already has the ORR on cohort 1. Seems suspicious to me.
As always excellent detailed analysis. We agree financing somewhere around mid-2020.
The elephant for me is Poziexon20 cohort 1 data reveal in 4th quarter.
If results are stellar (in eyes of the market), all will be well. If they are not, I think the PPS will take a major hit and they will be raising money in that environment.
Rolontis is a side-show until there is revenue clarity.
It bothers me that SPPI does not plan to show any data until 4th quarter.
TGTX just announced interim ORR data on a MZL pivotal trial.
IF you will indulge me. Now that I am mostly cash perhaps I am more critical.
Let's accept that SPPI has about $350M in cash and equity, with no clear revenue stream (a licensing deal or sale of Qap are speculative).
My estimate is that SPPI will burn about $200M per year. I have never seen SPPI allow cash to go below $100M.
So SPPI has about 5 or 6 quarters before they need new revenue, unless they sell or license something that may buy another quarter or so.
If Rolontis hits the ground running in 2020, all will be well, but if sales don't ramp up quickly to the $200M+ range, there will be problems.
Where is this wrong?
Thanks for your feedback. Agree with most of what you said.
I haven't given up on SPPI. I just readjusted my strategy as JT has changed the risk/reward calculus.
Just one mistake can take us down to the mid-single digits. Has SPPI ever made a mistake?
If SPPI get's away from me, I'm prepared for that. Already sitting on a nice profit.
Hi Antihama. Not sure if you are checking Yahoo board, but I just told them I sold 70+ of my SPPI. Actually its now over 90%. Will remain with small holding and add if situation improves.
Basically, I lost confidence in management for many reasons.
And without JT being explicit I got the sense that they will resist lowering the dosage in those "resistant" patients. Knowledge is power.
Nice summary: the dose reduction schedule management caught my attention.
Here is the summary of what I understood. There are a range of exon20 insertion mutation, some of these are highly responsive and some are a bit tougher. From Heymach team, SPPI knows which specific exon20 mutations are tougher. The dose reductions go from 16 to 14 to 12, and only with consent down to 10. The inference is that the trial PIs will try hard to maximize the dosing for the hard to treat mutations.
You have a difficult to treat mutation and are having some problems with dosing toxicity. The PI says to you, we really need to keep this dose as high as possible to maximize the efficacy. Can you handle the 12 mg?
Thanks. Just one more thing to worry about. Hehe.
If JT is right about Rolontis and Poziexon20, selling the drug portfolio is a major positive step. If he is wrong, he is a major fool who destroyed what Raj built (for better or worst) in less than two years.
I hope is that he knows that.
Nice thorough analyis of the Pozi BTD situation. I agree that SPPI could potentially refile for BTD designation, but not sure of its practical value.
I am more concerned that SPPI has a sober understanding of what the FDA wants to see in an accelerated approval filing based off cohort 1 data.
The last thing we want to hear is that SPPI will not file for BLA based on cohort 1 readout.
I'm confident that the ORR, DoR and DCR will be impressive, but have to take SPPI's word that it is what FDA needs for approval.
On pins and needles waiting for FDA to accept the Rolontis BLA application. Nothing is a given with SPPI.
Having two agents that attack the same receptor may be a problem. T-DM1 and Pozi both would hit the HER2 receptor on cancer and non-cancer cells. I don't recall seeing that many drug combination that hit the same target especially wherein they were both individually toxic to non-cancer cells. SO, I agree that toxicity could have been an issue.
I still think that MDACC and SPPI are looking for non-HER2 and non-EGFR targeting drugs as the companion drugs with Pozi. I know that Heymach likes Bevacizumab, but not sure what other candidates they have.
I also don't know if the phase I T-DM1 + Pozi trial in mBC would have given them any useful data for the exon20 trials.
As you said, we will learn more in 2H.
Up next is getting a PDUFA data for Rolontis.
I agree. I was thinking possible toxicity also.
But, why did SPPI say: for "strategic reasons"?
Pozi + T-DM1 for mBC was way off in the future as far as I understand.
If Pozi + T-DM1 has a toxicity issue in mBC, that may also be a problem in NSCLC.
My guess is they want to focus on Bevacizumab + Pozi for exon20 NSCLC.
We've been discussing on Yahoo, but no one knows why. Strategic decision could mean anything.
SPPI keeps tightening focus. Hopefully, they have good reasons.
Decaf just shared this list of mBC candidates: DS-8201, Tucatinib, Pyrotinib, possibly Neratinib. It is what I am aware of. I am sure, there are some others.
SPPI just terminated the Pozi + T-DM1 phase I combination trial. Decaf thinks SPPI may be abandoning mBC.
Antihama. Thanks for the detailed response. I haven't looked at mBC recently, so I need to catch up in this area. I'm not sure what competitor products are currently in development. Is Nerlynx one of them? TIA.
Antihama. Are you saying you expect Pozi Breast cancer data by MASCC June 21-23 and you expect PFS greater than 4.5 months? Just want to be sure I'm reading your post correctly.
I think genotyping is fast becoming a mandatory requirement just like cancer identification and staging before treatment.
It has already started in the well funded research institutions, but will quickly move into most regional cancer centers. There is just too much new cancer research and drug development that depends on genotyping. I expect that in just a few more years it will be routine.
I imagine SPPI is doing whatever they can to support genotyping access for the Pozi trial cohorts.