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Aptose Biosciences Inc. (APTO)

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3.4000-0.0700 (-2.02%)
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  • T
    Tartiaboy
    I have listened to the webcast 5 times and pored over the slides an additional five times. Here is my overall sense and summary.

    This is a dose escalation phase of Lux development. The focus should be on safety and tolerability. The good news is that there are no safety signals (so far) to prevent us from moving to 900mg. Barring a hiccup we should get to 900mg in NHL with the few weeks. Per the graph, I believe the final 750 NHL patient was only a week out from the 30 day cycle completion. Recruiting AML patients appears to be relatively easy because they are in desperate stage with few options. Consequently, I think AML will catch up to NHL at the 900mg level within several months.

    Clearing 750 will be very significant since it gets us to the 2 microM plasma level where true clinical benefit should begin to manifest.

    Regarding Responses: I agree with APTO the the signals are improving with every dose escalation. That said, few patients are staying on the trial at these lower doses making it difficult to assess low dose efficacy potential. Even at 750mg there are only three active participants-2 DLBCL and one WM (no CLL).

    What does this mean. To me it means that the story about Luxeptinib NHL efficacy is wide open. I don't think we will begin to understand Lux efficacy potential in NHL until sometime next year.

    AML is a different story. We had efficacy signal at 450mg including a CR. APTO has not reported on 600mg AML efficacy. That is a bit of a concern to me. I would have preferred some statement even if it was we will report regarding efficacy in the future.

    Regarding valuation: I think that it will depend mainly on what happens with AML throughout the year. BUT, I still believe we have a wide open question regarding Luxeptinib for NHL. We can hear the duck, we can smell the duck, we just can't see the duck (yet).

    Be First, be right (be patient).
  • S
    Sidney
    Looking more and more like a "lifestyle vehicle", which are notorious in small biotech. Meaning, these companies move at a snail's pace ON PURPOSE giving tidbits of hope along the way so management can collect hefty salaries to fund their lifestyles. If studies moved quickly and the ultimate rejection in Phase 3 was received, that would mean the company would fold and execs can't collect salaries. It should not take 3 years to do Phase 1 studies. Most phase 1 is done by 18 months maximum. My background: MD with 25+ years investing experience. Just a tip: avoid Canadian biotech.
  • T
    Tartiaboy
    So what is it going to take to get the markets attention in a positive way?

    Here is my speculation: A PR or CR in an AML patient with Ras mutations. I believe that one of the expansion cohorts in AML that APTO hopes to initiate 2H, is an AML cohort with Ras mutations. In some way I see this as analogous to what ARQL did with 531 treatment of RT.
  • T
    Tartiaboy
    Two of the three patients actively on 750 Lux are r/r DLBCL patients. APTO did not provide subtype information: whether they are GCB- or ABC- subtypes: Found this regarding non-GCB DLBCL.
    Down-regulation of cylindromatosis protein phosphorylation by BTK inhibitor promotes apoptosis of non-GCB-diffuse large B-cell lymphoma. Cancer Cell Int. 2021 Apr 7;21(1):195.01891-2.
  • T
    Tartiaboy
    The NHL waterfall plot shows FIVE cases of apparent tumor reversal. Four in CLL/SLL and one in FL. The FL reversal appears to correlate with dose escalation from 450 to 600mg-i.e. dose dependent. The four CLL/SLL reversals were seen at the 600 and 750 levels. CLL/SLL patient #9 started at 450 but was elevated to 600mg after cycle2.

    While we have no classical responses (PR, CR) yet there is clear evidence that tumors are beginning to show tumor size responses at the 600 and 750mg levels.

    While most of the literature regarding PsP in CLL is related to IO, this is a relatively newly recognized phenomenon and Lux has a potentially new mechanism of action. So, the concept of PsP being seen in this data is unproven, but not unreasonable. More clarity on this will likely be forthcoming.
  • T
    Tartiaboy
    Right now there are only six patients being actively dosed with Lux. Three are at 750mg: 2 DLBCL and 1 WM. There are three other patients at lower doses. 1 CLL/SLL; 1 FL and 1 MCL. If they stay on treatment APTO intends to elevate them to 750mg. Only two patients have been on any dose for over 3 months (patients 9 and 21). Both show signs of efficacy. Patient 9 is an SLL that has shown a tumor reversal. Patient 21 is WM with 25% reduction in % IgM.

    Based on the patient 5 data, it may take several months at sufficient dose to see PRs. We are just now getting to sufficient dose. The biggest takeaway (new learning) is that APTO needs to persuade the treatment givers to keep patients in the trial as long as possible.
  • T
    Tartiaboy
    Well wasn't that fun! I have listened to the webcast several times and continue to study the graphs and posters. We did not get bad data. We got data that did not meet street expectations-YET! I believe we are still on track, just a bit slower than we all want.

    Over the next week or so we can analyze the date in detail.

    I know it may sound like harping, but we are still dose escalating and just now entering efficacy dose range. I believe the clinical activity seen at 450 and 600 is very promising, but those doses are too low. My biggest fear is if we don't clear 750 which I see as the minimum RP2D. That's what I am most disappointed about. I expect we will clear 750 within the next month or so, but it needs to happen.

    Anyone who understands the multi-kinase concept and the nature of these diseases should understand my point. We need to achieve the IC50s of some of these other kinases to see dramatic effect in these r/r patient groups.

    If APTO can settle on an RP2D of 900 or greater I will be highly confident.

    I think we will go to 900mg in both AML and NHL in the near future. That's going to be big new (at least to me).
  • T
    Tartiaboy
    It will be interesting to see if APTO begins to monitor ctDNA in SLL/CLL patients. There are several studies that suggest that ctDNA may be a useful tool to tease-out whether an apparent tumor increase is due to PsP or to progression. Since this is a open question for APTO and since it would have a direct impact on decisions to continue or stop Lux treatment for a CLL patient, it seems appropriate. Watch for it.
  • T
    Tartiaboy
    I have been looking more closely at the slide six. The way this I read this is that we need to be at or above 2 microM Lux steady state to knock out the majority of CLL cells. Even that is not high enough to knock them all out. I say this because I am assuming that the CLL cells Lux is targeting may resemble the more resistant cell lines shown on the graph-i.e. those with IC50s over 1 microM. This may partially explain why we are just beginning to see tumor reductions in the 600 and 750 microM range. I believe that if we get an RP2D of 750 or preferably 900mg with a plasma steady state of 2, preferably 3 microM Lux as a single agent may kill 80% of CLL clones (but NOT ALL). This is not bad.

    Here is the good news. If we can achieve these levels of Lux in combination with Venetoclax I think we may see killing of 95% of CLL clones. This is where we really see benefit in this highly r/rCLL population. We will not have an answer to this until probably late next year, but I think it is one direction we may be headed for CLL.

    The point is right now we are developing the RP2D for Lux and showing that it has single agent activity. I do not believe APTO has any intention of developing Lux as a single agent. They expect it to be used in combinations.
  • T
    Tartiaboy
    Regarding CLL. I do not know how this will ultimately play out for r/r CLL. What I do know is that the treatment of r/r CLL is and will be done by combination studies. There is tremendous progress being made in that area. TGTX has some strong combination, MEIP has a best-in-class PI3Kdelta in development, ONCT has cirmtuzimab and CAR-T/NKs coming, and there are other drugs and combinations. So where, if at all, Lux plays in CLL is YTD.

    LUX is potentially powerful drug with a safety profile that may allow it to be combined with other drugs in new cocktails for CLL and other NHLs. Right now we are exploring the SAFETY profile and DLT, not efficacy. Look at how many different NHL types APTO allows on the trial.

    The focus is on getting to RP2D.
  • C
    Carol J
    Tiaraboy I dont care how many times you read the slides that Aptose has put together the FACT is that 806 and 253 has been ongoing for 3 years and they have only enrolled 9 subjects in a phase 1 study and has spent over 500M to date with little to no data or progress.

    They have not enrolled enough subjects in any of their studies to make any judgements, statements or validate the safety or efficacy of 806 or 253.

    You should all use your common sense and ask yourself why has these studies been going on for 3 years and they have not even completed enrollment.

    Most phase 1 studies are completed in 12-18 months while Aptose studies has only enrolled 9 out of the 161 subjects target in 3 years!!
  • T
    Tartiaboy
    50% of the patients treated so far were either r/r or refractory. That's a tough population to treat.
  • j
    jim
    $apto market cap of $500M this morning and it has a phase 1 aml trial / chemo that hardy works $sls AmL P3 just 6 months away from a fda approval and it trades for 1/3 !!!! Sls is undervalued!!!
  • C
    ChristianB
    The way this is going...yawn...I might be in a retirement home the day this will be profitable, if at all.
    Losing hope. Sorry.
    Bearish
  • T
    Tartiaboy
    Be First, be right (be patient). I have never seen a biotech that did not experience growing pains. All is well. Will let the dust settle for a day or two.
  • d
    dcaf7
    It is an interesting statement.
    "Based on the totality of our preclinical and clinical observations to date, we expect to select an expansion dose and expansion cohort strategy for AML during 2H21 and aim to explore select disease genotypes under monotherapy and combination therapy programs."
    Wonder what genotypes are they going to study?
  • d
    dcaf7
    It is time to analyze adverse events. From EHA presentation, Lux causes 41% of grade 3 AEs, including 23% of grade 3 neutropenia. In ARQ-531 trial this number is 19%, with 13% neutropenia. In Loxo 305 dose-escalation trial you can see only 8% of grade 3 AEs, with 5% neutropenia. Why I am focused on neutropenia. Because Lux is Flt 3 inhibitor. Treating AML with FLT3 inhibitors you cause myelosuppression and as a result, neutropenia. Why do you need double BTK/Flt3 inhibitor to treat B-cell malignancies and almost guarantee a neutropenia when you can avoid it using Arq-531 or Pirtobrutinib which are less toxic in general? With Lux dose-escalation, expect to see even more toxicity.
  • T
    Tartiaboy
    Regarding APTO-253, they have added several more dosing tiers, up to 403mg/m. That's three levels higher than current dosing level. Do not discount 253. It could become a big play.
  • d
    dcaf7
    Interesting view on BTK inhibitors.
    Low-dose Btk inhibitors: an ‘aspirin’ of tomorrow?
    "low doses of ibrutinib could prevent deep vein thrombosis"
    https://www.haematologica.org/article/view/10124
    Low-dose Btk inhibitors: an ‘aspirin’ of tomorrow? | Haematologica
    www.haematologica.org
  • B
    Brad
    looks like the price is going to drop today what do you guys think?