Protalex Inc. researching new and unique ITP and RA treatment.

I stumbled across this company while researching ITP after I was first diagnosed in April 2017. I have since purchased shares in the company and also this morning I sent them my contact info and asked them about their new patient trials (no reply as of yet, I just sent it). Below is a copy of their letter to shareholders sent out this morning 6/7/2017 and a link to their website if you would like to read more info. It is a good sign that somebody has adopted ITP and even if their treatment research falls flat there can be lessons learned from that.
To My Fellow Shareholders:

Protalex started 2017 with several advances to our global clinical development programs of our lead product, PRTX-100, a highly-purified form of Staphylococcal protein A (SpA), as a potentially safe and effective new treatment for autoimmune diseases, that position us for continued advancement throughout the balance of the year and beyond.

We continue to enroll our Phase 1/2 dose escalating studies of PRTX-100 as a potential new treatment for chronic immune thrombocytopenia (ITP) in the U.S. (the 202 Study) and in Europe (the 203 Study). To meet the challenge of patient recruitment associated with an orphan disease like ITP, we markedly expanded the number of clinical sites in both the U.S. and Europe. Last week we began patient screening in the United Kingdom to augment the 203 Study in Europe. With this expansion, we now have more than 20 sites worldwide open for patient enrollment.

The 203 study is an ascending dose phase 1/2 focused on adult with ITP who have failed one prior treatment. The 202 study includes adults with chronic ITP who have proven refractory to thrombopoietin agonists. We expect to complete the second cohorts of each of these studies shortly and look forward to advancing both studies to their third cohorts. For additional information on trial design and study sites, please visit www.clinicaltrials.gov .

We are encouraged by our initial results in both the 202 and 203 Studies, which thus far show an acceptable safety profile to support continued enrollment into higher-dose cohorts in both trials. We have observed two platelet responses, as defined per protocol, in the trials, as described in part in an abstract published for the American Society of Hematology conference in December 2016.

Regulators have granted PRTX-100 Orphan Drug Designation as a potential treatment for ITP in both the U.S. and Europe. This status provides commercial exclusivity benefits, tax credits for certain research, potential research grants and a waiver of the New Drug Application user fee in the U.S. Earlier this year, we applied for a $500,000 grant for our ITP trials with the Office of Orphan Products Development (OPD) in the U.S. Food and Drug Administration (FDA). We are pleased to report that our application received a Priority Score of 20, which is a competitive ranking as scores are graded 0-90 with zero being the highest score. We believe that we will likely receive the grant because scores better than 30 received funding in previous grant cycles. We will receive notification by the end of September and, if awarded, will receive the funds shortly thereafter.

We recently initiated a study of PRTX-100 in an animal model of Myasthenia Gravis (MG) and expect to have top-line results from that study sometime in the 3rd quarter of 2017. MG is an autoimmune disorder caused by anti-self antibodies that react with the neuromuscular junction causing muscle weakness and fatigability. MG remains underdiagnosed in the United States and has an estimated incidence of 14 to 20 per 100,000 population, thus approximately 36,000 to 60,000 cases in the U.S.1 Current treatments, which include corticosteroids and immunosuppressant agents, are not optimal as they can cause severe adverse events. As neurological autoimmune disorders in general lack efficacious treatments without adverse side effects, we believe that achieving positive results in the mouse preclinical model of MG could widely expand the development and application of PRTX-100 in other neurological autoimmune conditions.

We continue to invest in expanding our global intellectual property portfolio as part of our commitment to broadly protect our proprietary immunomodulatory SpA technology. We continue to fortify our patent estate to support our comprehensive strategy for the development and commercialization of PRTX-100 in a variety of autoimmune and inflammatory diseases. In the past year, we were granted seven key international patents that protect and expand the uses for PRTX-100 in autoimmune diseases, including rheumatoid arthritis (RA), ITP, and MG, among others.

We are especially grateful to the patients, clinicians, collaborators, and employees who have contributed to our progress and who will continue to help us succeed. We believe that the next 12 months will be a period of both confirmation of the safety and efficacy of PRTX-100 as a potential treatment for ITP, as well as one of expansion of its potential indications and uses.

On behalf of our Board of Directors and management team, I thank you for your continued interest in and support of Protalex as we advance our plans to bring potential new treatment options to patients suffering with autoimmune diseases such as RA, ITP and MG.

Sincerely,
Arnold P. Kling
President
www.protalex.com/

FYI, if you go to the bottom of this page:
clinicaltrials.gov/ct2/show/NCT02401061?term=PRTX-100&rank=4

it lists participating drug trial locations in U.S.

In other important topics, a couple of questions. With each of your Dex pulses your counts have been increasing? When you had IVIG how high did your counts go and how long did it take for them to fall back down to baseline?

Your responses seem to be good so far. What are your counts now?

Just wondering....if you are afraid of Rituxan, why would you want to try something that has potential unknown side effects?

And welcome!

My experience since 4/24 when I was diagnosed has been higher highs and higher lows. My last (4th) round of Dex ended 5/26/17 and also was 14 days post 3rd IVIG when I had a 217 high! In 4 days I dropped to 192, 3 days later 170, 4 days later 152, 3 days later 141, at that time we cut back to being checked once a week, that first weekly check was yesterday and after 7 days I was 138! having only dropped 3,000. We are ecstatic! As far the potential side effects of the new treatment the company published this after their last trial " PRTX-100 exhibited an acceptable safety profile and RA disease activity was improved in a majority of patients at the end of the study as compared to baseline. No serious adverse events (SAEs) were reported. " In comparison to 3% or Rituxan users dying after first dose, 17% developing permanent lymph node issues, and having only a 38% success rate after one year. Yesterday I was notified I do not yet qualify for the study as they are only accepting those that have failed on Rituxan, n-plate, promacta or other post steroid treatments. After 3 weeks post dex I can finally tie my shoes, that messed me up.

I'm not advocating Rituxan, but generally the patients who died or had complications had other serious health problems going on. I do understand your hesitancy though; Rituxan is a heavy-duty treatment. Many people have had success with remissions, but as you said, they generally don't last longer than a year. Some have had remissions lasting several years.

Higher highs and higher lows? BUY, errr ahh I mean, sounds great thomasak. Hope it turns into remission.

Folks I've seen on PDSA with a strong steroid & IVIG response seem to have done well (remission) with Rituxan. I wonder if that characteristic will be true with PRTX-100 as well. Do you suppose it acts on the B cell like Rituxan does - just safer somehow? Both are four treatments once a week.

Hal - I couldn't get enough info to figure out how it works. All I could find is that it is 'a formulation of a proprietary, highly purified form of Staphylococcal Protein A, which is an immunomodulatory protein produced by bacteria. PRTX-100 has the ability, at very low concentrations, to bind to human B-lymphocytes and macrophages and to modulate immune processes. The safety, tolerability and pharmacokinetics of PRTX-100 have been characterized in five clinical studies. In two Phase 1b clinical trials in adult patients with active RA, PRTX-100 was generally safe and well tolerated at all dose levels, and at certain higher doses, more patients showed improvement in measures of RA disease activity than did patients at the lower dose or placebo cohorts.'

www.protalex.com/about/overview

Ha, they say that Dex is 'well tolerated' too.

Here is more:

Background: In idiopathic thrombocytopenic purpura (ITP), autoantibodies bind to platelets which are then phagocytosed by monocytes/macrophages and removed by the reticuloendothelial system. PRTX-100 (Staphylococcal protein A) is being investigated for the treatment of ITP.

Objective: To assess the effect of PRTX-100 on phagocytosis of platelets in an in vitro assay.

Methods: Human monocytes were isolated from whole blood peripheral blood mononuclear cells (PBMCs) by adherence and cultured for 6 days in RPMI + 5% human serum. 48 hours prior to phagocytosis assay, PRTX-100 was added at 250, 25, and 2.5ng/ml. Human platelets were labeled with a fluorescent (PerCP) lipophilic dye and opsonized with an antibody to MHC Class I (W632). 2×10−5 monocytes were co-cultured with 2×10−7 labeled platelets for 1 hour at 37 ° C. All conditions were performed in triplicate. After an hour, phycoerythrin (PE) labeled anti-CD61 antibody was added to assess surface bound platelets versus ingested platelets. Phagocytosis was determined by flow cytometric analysis. The monocyte population was gated upon by forward and side scatter properties, then verified by staining with CD14-FITC. Percent phagocytosis was calculated as the fraction of ingested platelets (PerCP +/CD61−) to the total PerCP population (PerCP +/CD61−) + ( PerCP+/CD61+) within the gated monocyte population.

Results: PRTX-100 inhibits the phagocytosis of W632 opsonized platelets by human monocytes. Phagocytosis of W632 opsonized platelets was 40%, while phagocytosis in the presence of PRTX-100 at concentrations of 250, 25, and 2.5ng/ml was 18.3%, 23%, and 24.3%, respectively. Phagocytosis at 250ng/ml and 25ng/ml was significantly different from control phagocytosis with p values of 0.014 and 0.001 respectively by Student’s t test.

Conclusions: PRTX-100 inhibits the phagocytosis of platelets by monocytes, the effector limb of ITP. Prevention of platelet phagocytosis is an important treatment goal in ITP. PRTX-100 has been shown to be generally safe and well-tolerated in a phase I study in healthy volunteers (J Clin Pharmacol, in press). PRTX -100 is a promising therapeutic option for ITP and deserves further study.
www.bloodjournal.org/content/108/11/1081?sso-checked=true

I guess this drug has been around for awhile. That study is dated 2006. I was expecting a follow up post describing how it works in laymen terms but that never happened. :lol:

Recall that Rituxan works via CD20 opsonization. This drugs seems to have a totally different mechanism. It acts on MHC Class I (W632) on the platelet surface. No B cells are destroyed. Just phagocytosis of platelets is reduced/blocked.

I found this 2015 study: "Successful Treatment of Thrombocytopenia with Staphylococcal Protein A (PRTX-100) in a Murine Model of Immune Thrombocytopenia (ITP)"
www.bloodjournal.org/content/126/23/1045?sso-checked=true
Here one can see in Table 1 that PRTX-100 is compared to IVIG. So there it is. It acts like IVIG in terms of platelet response but blocks a specific platelet label-for-destruction pathway - instead of overwhelming all phagocytosis as IVIG seems to do.

Finally, there is this 2016 study: "Safety and Efficacy of PRTX-100, a Highly Purified Form of Staphylococcal Protein A, in Patients with Immune Thrombocytopenia (ITP)"
www.bloodjournal.org/content/128/22/4929?sso-checked=true
One can see in Figure 1 the platelet count response graph of a patient who has responded to a very low dose to the drug. I suppose higher dose studies are being performed now.

Perhaps this drug may be best suited as a replacement to IVIG especially when treatment needs to be given regularly and continuously. Many ITP'ers are in that boat and I guess perhaps even more Rheumatoid Arthritis suffers are as well.

Have I got it?

I don't know. I would like to see more information, mainly, ingredients.

This has been around for 11 years and is still in clinical trials? That seems odd. I know it takes time, but that is quite a while.

I would classify PRTX-100 as a "drug looking for a disease" The company has been throwing this like a dart at the wall to see what it will stick to. If what they have published so far can be interpreted as effective against RA, ITP, MS, and others this could be the biggest drug since aspirin. I remain hopefully skeptical

Sounds a bit like Fostamatinib.
Failed for Rheumatoid Arthritis, 18% response rate for ITP, now being trialled for IgA Nephropathy & Haemolytic Anaemia

And this article for Fostamainib touts 'top line results' for RA.

www.centerwatch.com/news-online/2013/04/05/astrazeneca-touts-top-line-results-from-oskira-1-phase-iii-study-of-fostamatinib-in-ra/