Ann: Successful Meeting with FDA on Phase III Design in NSCLC, page-10

Healthcare Immutep: Positive Efti Treatment Data Leads To Late-Stage ProgramsJul. 15, 2024 1:54 PM ETImmutep Limited (IMMP) StockMRK, PRRUF2 CommentsTerry ChrisomalisInvesting Group LeaderFollowPlay(17min)SummaryImmutep Limited achieved positive results in the phase 2b study, using efti + Keytruda for the treatment of patients with 1st-line head and neck squamous cell carcinoma; Both PD-L1 positive and negative patients.Company to meet with FDA to be in a position to initiate a phase 3 study using efti + Keytruda for the treatment of patients with 1st-line HNSCC.Merck supply collaboration agreement in place to advance phase 3 study, using efti + Keytruda + chemotherapy for the treatment of 1stline NSCLC patients.Keytruda had become one of the top-selling drugs in 2023, with sales exceeding $25 billion; Efti has shown to help double several efficacy measures when added to Keytruda.I am Terry Chrisomalis, a long term Biotech investor with a degree in Applied Science. I am the leader of the investing group Biotech Analysis Central, where I analyze high risk/high reward ideas. Jacob Wackerhausen/iStock via Getty ImagesImmutep Limited (NASDAQ:IMMP) recently reported results from two cohorts from its phase 2b TACTI-003 study using efti [eftilagimod alfa] for recurrent/metastatic 1st-line head and neck squamous cell carcinoma [HNSCC] patients. The first set of results was based on this entire patient population, regardless of PD-L1 expression. The other set of positive results released a few weeks later was based on this same patient population, but for such patients with negative PD-L1 expression. With this positive data on hand, this biotech is going to approach the FDA to get a phase 3 study going targeting one or both of these 1st-line HNSCC patient populations.This is one program, which is already moving towards late-stage development. One other program, already underway in phase 3 testing, would be the phase 3 TACTI-004 trail. This specific late-stage study is using efti in combination with Keytruda + chemotherapy for the treatment of patients with 1st-line non-small cell lung cancer. Both of these programs are being done as a supply collaboration agreement with Merck (MRK), where this big pharma is providing supply of Keytruda to run these studies. Immutep still retains rights to efti for now.Efti is a versatile drug in that it could also be combined with chemotherapy or other agents to treat other cancer patient populations. It is currently being explored in the phase 2/3 AIPAC-003 trial in combination with weekly doses of paclitaxel for the treatment of patients with metastatic breast cancer. Data from the randomized portion of this specific trial is to be released at some point in 2024 and would not only provide shareholders with another catalyst, but also possibly, another shot on the goal for efti advancement. Efti has also shown in several other programs besides the ones noted above, and there is massive potential for this specific drug in Immutep's pipeline.HNSCC Treatment Program With Efti Moving Towards Late-Stage DevelopmentAs I noted above, a good thing about Immutep is that it already has an extensive clinical trial supply collaboration agreement with Merck. This, big pharma is providing Keytruda towards several studies so that it can be combined with eftilagimod alpha [Efti]. The main premise of this solid molecule is that it is a LAG-3 protein and MHC Class II agonist. The goal of this LAG-3 protein is to drive affinity towards MHC II class antigen-presenting cells to activate both the innate and adaptive immune system to target and killer cancer.How does this Efti drug differ from other immunotherapies or anti-PD-L1 treatments like Keytruda? That's because Efti is capable of targeting the MHC II class on multiple APCs beyond T-cells like: CD4+ T-cells, CD8+ T-cells, Natural killer [NK] cells, dendritic cells, monocytes plus many others. Whereas Keytruda targets T-cells. However, when Efti is combined with Keytruda, this leads to a more pronounced effect. One in where there is an ability to go after all tumors regardless of PD-L1 expression status. This lays out the foundation for Efti to be combined with PD-L1 inhibitors to enhance the ability to effectively treat all types of solid tumors. Especially, in patients who fail on PD-[L]-1 therapies.Keytruda had become one of the top-selling drugs in 2023, with sales exceeding $25 billion. Where does Efti fit in? Well, Efti in combination with Keytruda has been shown to more than double multiple measures in clinical testing in solid tumor patients. Such as doubling of: Overall survival [OS], Progression-free survival [PFS], overall response rate [ORR] and deeper durable response.Having said all of this, this sets up Immutep with a few good late-stage program opportunities. The first late-stage program opportunity would be regarding the use of efti in combination with Keytruda for the treatment of 1st-line recurrent or metastatic head and neck squamous cell carcinoma [HNSCC]. This would be regarding the recent positive results released from the phase 2b TACTI-003 trial, which explored the use of this drug for the treatment of this patient population in two different cohorts.The two different cohorts deployed for this specific study targeting this 1st-line HNSCC patient population are as follows:Cohort A : Efti + Keytruda versus Keytruda alone as a monotherapy in patients with PD-L1 positive HNSCC tumorsCohort B : Efti + Ketyruda to treat PD-L1 negative HNSCC tumors.One immediate thing to point out is that Cohort B had no randomization in place at all. Why is that? That's because Keytruda is not approved as a monotherapy to treat PD-L1 negative 1st-line HNSCC patients. Thus, it was inappropriate to randomize this specific arm of the study.Before going over the clinical data, it is also important to note what each PD-L1 status refers to. When talking about PD-L1 positive patients, these are patients whose tumors' Combined Positive Score [CPS] is ≥1. Thus, this is simply referred to as being PD-L1 positive. On the other hand, regarding PD-L1 negative expression patients, their CPS score is <1.The thing is that the overall response rate was seen to be superior in the efti combination arm compared to the Keytruda arm across all levels of PD-L1 expression. This was as follows:ORR of 32.8% for efti combination armORR of 26.7 for Keytruda arm.Not bad when you consider that any improvement here is ideal. However, an even more notable separation was observed in these 1st-line recurrent/metastatic HNSCC patients who had a CPS score of >20. What does this CPS score indicate? This means that these patients were high PD-L1 status. With these patients with high PD-L1 expression, the data improved compared to what I just displayed directly above in the patients with all levels of PD-L1 expression.The data achieved using the efti combination arm for the patients with a CPS score of >20 was as follows:ORR of 31% for efti combination armORR of 18.5% for Keytruda arm.As you can see, the efti combination fared much better when patients had a PD-L1 high status with a CPS score of >20.While this data from the portion of the study targeting PD-L1 high positive HNSCC patients is good, there was another data release which showed the efti combination to perform well in PD-L1 negative status expression patients. The results, released from this portion of Cohort B of the phase 2b TACTI-003 trial, showed that the efti + Keytruda combination were able to achieve an ORR of 35.5%.Why was this a highly impressive outcome? There are two reasons why this was a good data outcome. The first of which is that this was the highest ORR observed in PD-L1 negative 1st-line HNSCC patients [CPS score of <1] without chemotherapy. Consider that historical control for this specific patient population shows an ORR of 5.4% for those given anti-PD-1 monotherapy. The second reason of which would be the fact that there were actual complete responders. In relation to this, the efti + Keytruda combination treatment resulted in a 9.7% [3 out of 31 patients] Complete response [CR] rate. Whereas, ant-PD-1 monotherapy historical controls show a CR rate of 0%.With all of this positive data on hand, the next catalyst to expect with this program would be the initiation of a phase 3 study. There are a few paths here for this program, and this would be because of the data obtained. There is an ability to discuss a path forward targeting a broad PD-L1 1st-line recurrent/metastatic HNSCC patient population [regardless of PD-L1 status] or to go after such patients with negative PD-L1 expression [CPS <1]. Thus, if talks go well with the FDA about this HNSCC treatment program, then a phase 3 study should be the next catalyst for investors to expect here.Merck Supply Collaboration Agreement is Highly Ideal For Late-Stage AdvancementThe above program of efti in combination with Keytruda is under the clinical trial collaboration agreement established with Merck. However, there is another program which is much further along. This would be regarding the use of efti in combination with Keytruda + chemotherapy to treat patients with 1st-line non-small cell lung cancer [NSCLC]. This triplet combination will be a giant study for investors to look forward to. That's because it will not be focused based only targeting a subset of PD-L1 status patients, instead it is going to target the entire 1st-line NSCLC patients regardless of PD-L1 status. The goal is to establish a new standard of care [SOC] for these patients, in hopes of improving response rates and prolonging responses for them.A positive new development regarding this program is that a clinical trial collaboration supply agreement with Merck for this phase 3 TACTI-004 study was achieved back on June 3rd of 2024. The good thing about this agreement is that both parties will retain the rights to their drugs, respectively. Should this late-stage study end up being successful, though, there are two highly important events to come about. The first event, which I noted above, is the potential for efti + Keytruda + chemotherapy to become the new SOC for these 1st-line NSCLC patients irrespective of PD-L1 expression. The second thing to come about is a possible partnership. Why do I believe that to be the case? That's because Merck is likely going to want to maintain its dominance, with Keytruda being dominant in NSCLC.If somehow Immutep Limited pulls superior data on certain efficacy measures, then I believe Merck might be inclined to generate a broader deal with payments. This is not guaranteed to happen, but quite possible if highly positive data is obtained in the phase 3 TACTI-004 study. This trial is expected to enroll a total of 750 NSCLC patients regardless of PD-L1 expression. In addition, the primary endpoint will be a dual one, looking at both progression-free survival [PFS] and overall-survival. Investors typically have to wait an extended period of time to see data, but the good news is that there could be quicker milestones to look forward to. This study is going to have a prespecified futility boundary analysis [likely to determine if the trial is to meet the goal] and pre-planned interim analysis as well.