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an identified contributor  Tal Ben-Ami began the following way:   

(Editors’ Note: This article covers a micro-cap stock. Please be aware of the risks associated with these stocks.)

Yesterday, Senesco Technologies (OTCQB:SNTI) reported positive results on its long-awaited cohort 3 in its phase 1b/2a trial for SNS01-T, an apoptosis-inducing cancer treatment being tested for multiple myeloma and diffuse large B-cell lymphoma [DLBCL]. Senesco followers have been awaiting this announcement for months now, and some investors expected a pop in SNTI shares if positive results were reported. They were indeed, though the stock actually reacted negatively, down $0.58 to $4.87 on volume twice above average, a drop of over 10%. What happened? First, some details on the trial and SNS01-T.

The main emphasis of Senesco is on ‘controlled apoptosis’ which means either speeding up the programmed cell death known as inducing apoptosis or slowing down the programmed cell death, which can be referred to as inhibiting apoptosis. Where inducing apoptosis can be used in treating cancer, inhibiting apoptosis has its applicability on wide range of inflammatory and ischemic diseases. It does this by controlling different versions of proteins that can either promote cell death or inhibit it by adding different amino acids to the ends of these proteins.

Senesco has developed a therapeutic candidate, SNS01-T, which is an upgraded form of its prior formulation of SNS01. SNS01-T focuses on treatment for multiple myeloma and non-Hodgkin B-cell lymphomas. It consists of three main components. The first one is an inhibitory RNA, which controls the hypusinated form of the apoptotic protein the drug is designed to control. Hypusine is an amino acid that when attached to the protein, inhibits apoptosis. The 2nd component is a plasmid DNA, which encodes the lysinated version of the protein (lysine is a different amino acid), a complex called EIF5A (Factor-5A), resulting in inducing apoptosis, or cell death. Finally, the 3rd component is a polyethylenimine nanoparticle, which protects the RNA and DNA in blood from getting manipulated by these drugs, basically protecting healthy cells while leaving cancer cells exposed.

This sounds like a lot to swallow, but the basics are this:

1. Component one inhibits the protein that promotes cell life
2. Component two promotes the protein that promotes cell death
3. Component three protects healthy cells from being affected

Where SNS01-T Differs from Immunotherapies

Much attention in the oncological world lately has been given to cancer immunotherapies. SNS01-T is not included in this, since it is not seeking to trigger any kind of immune response. The approach here is much more direct, as the drug itself is being used as a trigger to program cancer cell suicide, rather than activate the immune system against it. The approach here is fairly similar to Novartis’ cancer ‘miracle drug’ Gleevec, or imatinib for chronic myelogenous leukemia [CML], a tyrosine kinase inhibitor that, by stopping a protein cascade necessary for cancer cell growth, triggers apoptosis in these cells. As the CML cancer cells are the only ones to have this protein, they are the only ones affected.

Where SNS01-T differs from Gleevec is Gleevec wasn’t designed to specifically promote apoptosis. Rather, it was designed to inhibit cancer cell growth. Once cell growth is inhibited, apoptosis is induced as a response by the cell. (For Star Trek fans, picture the Borg Ship detonating itself after it sensed that the Enterprise had infiltrated its regeneration systems.) SNS01-T, by contrast, is specifically designed to activate genes within cancer cells that trigger apoptosis directly, instead of as a welcome side effect.

Progress with cohorts, and why the drop?

Senesco just completed cohort 3 for its phase 1b/2a trial. This is a dose escalation trial for SNS01-T attempting to show that the drug is safe and well tolerated. The safety profile of this drug is crucial, as it functions by directly attacking cells by inducing their suicide, and if the polyethylenimine nanoparticle does not function correctly in protecting healthy cells, there could be serious side effects with healthy cells committing suicide in droves. So far, however, so good, and no serious side effects have been reported.

SA author George Ronan, linked above, said the following about cohort 3 and SNTI stock:

The third cohort is underway, and Senesco expects to report its results by the end of this year. I expect this to be the catalyst that finally reverses investor sentiment. The reason for this is that the first two cohorts involved extremely low doses, 0.0125 mg/kg and 0.05 mg/kg, respectively. The third and fourth cohorts involve much higher doses, 0.2 mg/kg and 0.375 mg/kg, respectively.

Clearly investor sentiment has not been reversed yet, and I believe the author overlooked one small detail, which can be seen in the company’s latest press release about cohort 3. Namely, the significant tumor shrinkage that was seen in preclinical studies for SNS01-T took place at a dose of .375mg/kg, and cohort 3 only took doses of .2mg/kg. In other words, this cohort was designed to show safety at the .2mg/kg dose, not significant tumor shrinkage. That remains for cohort 4, which will dose at .375mg/kg, following which tumor shrinkage is expected to be seen.

The reason I believe SNTI reacted so negatively to the positive news around cohort 3 is that investors were probably expecting something more than just safety and stable disease. 2 of 4 patients in cohort 3 showed stable disease by the end of treatment, and one with DLBCL showed tumor shrinkage in some lesions. 6 to 9 patients are expected to be enrolled for cohort 4.

If those patients show significant tumor shrinkage with no serious side effects, then you’ll start seeing SNTI move. Safety alone is just not enough to get investors excited about a trial stage company.”

 

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