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Sorry we are past the stage in this market where a positive trial anouncement garners much of a sustsained pop. Future (in that case distant future earnings) are being heavily discounted. An earnings anouncement showing tangible traction in parasortix sales would help. The more granularity on the repeatability the better. Citing major pharma collaborations is good, indicating AZN or NVS incorporating parasortix on the front end of cell therapy or a CDX would be much better since it infers incorporation into a process leading to widespread sales and eventual profits. Same for diagnostic partnerships. The market wants to see a clear path to profitability. Everything else is being assumed to be smoke and mirrors.
FL
On the diagnostic front. I think the key for Angle is to keep the focus on sample enrichment services. If they keep the price point right, I think they can become the go to partner for all PCR based oncology testing and I would not be surprised if NGS testing would not benefit as well. This market is ripe for a better way to acquire higher quality circulating tumor samples.
FL
FL
Circulating Tumor DNA MRD Testing to Personalize Adjuvant Therapy for Stage II Colon Cancer
Precision Oncology News Webinar
Date: September 22, 2022
Time: 6:00 am PT / 9:00 am ET
The minimal residual disease, or MRD, testing landscape shows tremendous potential for improving treatment management and patient care. In this webinar, Afsaneh Barzi and Jeanne Tie will discuss the clinical utility of MRD testing for treatment management in patients with stage II colon cancer. Topics include the current standard of practice and guidelines for the disease, as well as existing evidence for detecting residual and recurrent disease by ctDNA analysis and how testing can be leveraged in a clinical setting. Real-world case studies will be presented in addition to perspectives on what the future may hold for MRD testing.
REGISTER HERE
Afsaneh Barzi, MD, PhD
Associate Professor of Medical Oncology
City of Hope Comprehensive Cancer Center
Jeanne Tie, MD, MBChB
Lower Gastrointestinal Medical Oncology and Trials Lead,
Peter MacCallum Cancer Centre Senior Research Fellow,
Walter and Eliza Hall Institute
I realize Angle does not have any current CRC studies nearling completion. However, this is just one of many cancers that are becoming engaged in circulating tumor monitoring. Angle may very well be at the crossroads by providing critical blood based sample enrichment services to dozens of companies providing cancer diagnostic, surveilance and monitoring tests.
FL
BoJo
Agreed. Having live circulating tumor cells is great for any technology that requires such cells (cell therapy, radioliganf therapy, etc) but I think the most readily accessible current market for Angle is for providing the upfront sample (circulating tumor concentrated blood) for MDx analyses. There are already a lot of players that market drug companion diagnostic tests that identify the molecular pathway that is actionable (i.e., drugable). Angle has the potential to improve the sensitivity of oncology PCR testing by concentrating the MAF of the samples undergoing molecular diagnostics. If Angle can scale up to lower the cost of sample acquisition, it could be huge on the front end of the MDx process.
I'm uncertain of the cost breakdown as to how much is related to the parasortix enrichment process and how much relates to post enrichment microscopy (cytology, cell counting etc) to generate a report. I can see a scenario where an oncologist may only want to pay for the lab report once but wants access to the the enriched sample for MDx monitoring of a patient.
FL
Thanks Thompi,
I'm primarily interested in parasortix ability to enrich the tumor content in a sample so that the mutant allelic fraction might better be analyzed by PCR. This is where it has synergies with my other investment. Alot of the drugs are effective up until the cancer develops a resistance mutation. BCART is partnered to develope a rapid CDx for AZN's NSCLC drug Tagrisso. I think the end market is to have an oncologist take a blood sample in the office and determine whether the medication is still effective or whether mutations have developed which would require another course of treatment. If parasortix and Idylla were somehow partnered, it might be possible to get that answer in a day as opposed to the standard NGS turnaround of about 3 weeks. I'll take your advice and pose some of these questions to IR.
Regards FL
Collecting a whole living tumor cell may have great utility for pharma cell therapy but I beleive their is also utility in molecular diagnostics (MDx). Parasortix can be useful on the front end in collecting a ct sample more easily than a biopsy. The analysis of this sample can then be used for a variety of purposes including companion diagnostics (CDx). That is why I believe that Qiagen was one of Angle's early partners. I think the key for Angle is to keep the price point where it becomes the hands down best option for obtaining biopsy samples for certain cancers. It seems that Angle is not fully into production mode. They have created a prototype manufacturing process that has not been fully scaled. Anyone on the board have a feeling about when they fully scale where parasortix pricing might be.
Also, I have questions on the lab portion of the analysis and the associated pricing. If parasortix harvests the circulating tumor, is the lab analysis similar to cytology using microscopy to identify the ct content. If your monitoring an existing cancer patient with a known mutation, can the angle lab analyses be skipped and the ct rich sample used for input directly into a PCR or NGS analysis?
FL
NGS is great for analyzing the whole genome and determining potential targets but once a specific molecular pathway is identified and under treatment, PCR can provide a more cost effective and timely means for monitoring for mutations that might render a specific drug ineffective. I beleive there are complimentary uses for the different technologied if the price points work out.
FL
I think Angle might provide a good fit with BCART. Their Idylla platform primarily uses FFPE tumor samples but the cartridge system has been demonstrated to be effective analyzing ctEGFR, ct RAS, ctKRAS, ctBRAF. The cartridge and instrument do the necessary DNA extraction so the sample input may be a FFPE sample or a blood sample containing sufficient ct content. To date one of the cheif problems with Idylla is that it is not as sensitive as NGS (Oncobeam) to low mutant allelic fraction (MAF) in the blood sample (see article). This makes the Idylla analysis of samples <5% MAF less accurate than Oncobeam. However, Parasortix appears to provide a means to increase the MAF in the sample used for analysis. Correct me if I'm wrong.
LifeArk and BCART will launch a breast cancer assay in the near future (a month or two). Now that Parasortix is approved for breast cancer in the US I think they should evaluate the use of parasortix for monitoring breast cancer from ct content in blood samples. There seems to be a strong synergy here but the cost of breast cancer assay on top of parasortix harvesting of ct may be too high of a price point. If they develop a partnership, I can see application in NSCLC, etc. I've attached a few articles.
I recently bought a small Angle position on US pink sheets, painfully illiquid so my only way out might require Angle catching fire. Neither of my brokers Schwab or IBKR would allow purchase through their international trading platforms. Both of these positions are total speculations.
FL
but it is not as sensitive to low alliel
https://finance.yahoo.com/news/press-release-biocartis-group-nv-050000031.html
https://www.nature.com/articles/s41598-019-45616-y
https://www.oncotarget.com/article/21476/text/
https://www.genomeweb.com/scan/lung-cancer-response-checkpoint-inhibitors-reflected-circulating-tumor-dna#.YvqIV3bMIb4
I don't find this result surprising. As I indicated before, I can see a possible role for Parasortix in mutation monitoring. I think the same results found for checkpoint inhibutors will be found for other mutation drivers. Thus, ctDNA may well become the prefered method for patient disease monitoring. I think the cost of repeated NGS analyses would be prohibitive for most insurers/payers. A combination of Parasortix and PCR sequencing for EGFR, ROS, Alk etc should be much quicker and cost effective.
FL
Chaz & BOJO, Thanks for the responses. I'll review the info. There are a lot of MDx companies that have really interesting science but are far from profitability. What I like about ANGLE is that it is complementary to many current run analyses and mostly seeks to improve the ease of monitoring. Its competitors are primarily the breast lumpectomy biopsy, prostate core biopsy and the large number of procedures used for NSCLC (most of which provide poor quality and insufficient sample). When viewed in this this surgical procedure avoidance manner, there can be a strong case for cost savings
when seeking insurance reimbursement. This can help traction during launch.
FL
Now that all the premium from the FDA approval for Parasortix Breast has been wrung out of AGL, I'm wondering what catalysts are on the horizon? I expect that announcements of partnerships with PCR oncology testing firms are forthcoming in next 6 months. I'm envisioning that these relationships will focus on disease monitoring possibly as a modification to an existing CDx. This type of testing would primarily look for genomic mutations that would render a treatment ineffective. Seems like this can progress rapidly for Breast cancer where the system has FDA validation.
Pharma announcements may also occur but these relationships may also remain confidential since cell therapy is pretty competitive.
So what other major catalysts are on the horizon (i'm pretty new to AGL so please excuse my lack of complete due diligence)? I see that a prostate cancer trial is underway in the Mid Atlantic US. If this trial is successful, how long would it take before the company files for any approvals (US, EU, etc). I read about NSCLC research, Parasortix could be extremely valuable in monitoring gene fusion and EGFR mutations. Any guesses how long for this to play out with FDA and EU registration filings? Similar questions about ovarian cancer etc.
Finally, does anyone have any thoughts on how advanced a breast, prostate or lung cancer has to become before measurable circulating tumor content can be harvested and detected in the bloodstream? I'm invested in other areas of MDx and see synergies but these types of things sometimes take years if not decades to play out, so I thought the board might have some insights.
FL
Angle may have a big edge in the CTC Capture and Harvest but it is far from capturing even a fraction of the analysis market. NGS, PCR, ddPCR, Fish etc technologies are all positioned to analyze CTCs. I believe that Angle should forgo any effort in the analysis area since it is expensive, very crowded with very few profitable companies. Instead they should license and sell the the CTC harvesting technology to the multitude of companies seeking to analyze CTC for MDx purposes.
FL
Please excuse me if the view from across the pond is far astray. It seems that given DHSC abysmal record in the pandemic including the purchase of questionable Chinese testing supplies, I would not be surprised if this whole dispute was more about leverage and keeping an innovative testing company from being bought out during the pandemic. I think the claim did a pretty good job of scaring away potential suitors. What was the figure GM originally felt the claim warranted. 20 mil I believe. They have made concessions that are more than adequate, I believe.
FL
I think the article misrepresents things. But frankly I'm new to AGL, so correct me if I'm wrong. The article laws out the costs comparisons relative to Guardant and Foundation (Roche). In my mind both of those comparison tests provide actionable genomic target information. AGL is not providing that kind of data. Rather the comparison should be to the cost of the lumpectomy procedure or prostate biopsy, etc. I think the future for AGL could be very bright if they focus on reducing costs for the cartridges and focus on replacing
FFPE tissue samples. The procedure could be a precursor to most if not all PCR oncology MDx analyses. But the costs right now are about equal to the PCR MDx analysis. So it doubles the costs compared to NGS.
FL
I agree with the comments about the primary value of liquid biopsy being monitoring. Initial characterization is most likely to be conducted using NGS for whole genome sequencing. Once the genomic driver is characterized targeted analyses looking at mutation panels (EGFR, ALK ROS, etc) are likely to be conducted for the mutation analyses. However, it is tough to get good quality samples without considerable expense. Lung biopsies to get solid tumor samples is prohibitively expensive. Cytology or lung brushing or swab samples frequently lack sufficient sample or the cancer cell content is limited. If parasortix can provide enriched CTC from easy to obtain blood samples I think it would be a big positive for monitoring genomic markers for mutations. This could provide critically timed data to determine when medications should be changed. My big question is still whether half the samples possessed little to no ctcs for Parasortix to collect (i.e., early disease) or whether the Parasortix design needs to be altered for the specific NCLC tumors (i.e., missing the circulating tumors).
FL
Todays RNS was missing a very important detail. While the RNS indicates that Parasortix was successful in collecting and enriching CTC in 50% of the samples it does not correlate the data to the stage of cancer. Did it fail to collect CTCs in 50% of the analyses because the cancer was earlier stage and not yet penetrating the ephithelial cells lining the blood vessels in the lungs? Or is it because the CTC from NSCLC are not as easily captured captured as the breast cancer cells?
FL
I follow another company that is active in microfluidic IVD applications (BCART out of Belgium). It has interesting technology that is akin to Cepheid GenExpert infectious disease cartridge business but with a focus on Oncology MDx. BCART as an investment has been a train wreck despite providing results faster, with less technician time and cheaper in most cases. The attached link discusses the major limitation to the use of BCART's Idylla system. The chief problems with the Idylla liquid biopsy is that it is not as sensitive to lower circulating tumor levels. It does perform very well when analyzing solid tumors or high circulating tumor liquid biopsy samples. NGS methods such as OncoBeam greatly outperformed Idylla for liquid biopsy samples with MAF <5% (see link). Now that Parasortix has been approved by FDA for harvesting and enriching the circulating breast cancer so they can be undergo further analysis. It appears that Parasortix could be instrumental in providing a better input sample for liquid biopsy analysis.
As I look at Angle's opportunities, I wonder if they would be more successful selling the cartridge as precursor to liquid biopsy IVD analyses or licensing the technology for use as part of the IVD analysis.
BCART has a partnership with LifeArc (a UK research venture) for development of the ABC breast cancer assay. It is supposed to be released for RUO use later this year for use on solid tumor samples. I would not be surprised if discussions are underway for use of Parasortix for a liquid biopsy version of the assay. Interesting possibilities, but as pointed out on this board it will likely take years to develop.
https://www.nature.com/articles/s41598-019-45616-y
FL
Please excuse me, if my being new to Angle results in stupid questions (i.e., ones for which most of the board already knows the answer).
Given that the FDA approval removes the primary barrier to marketing Parasortix in the U.S. what is the current production capacity for the microfluidic cartridges? Where is this capacity -UK or North America? I'm in the U.S. and don't believe that Angle could have pursued Medicare or private insurance reimbursement approvals or codes prior to receiving the FDA marketing approval. Anyone have any idea of what the breast system is likely to cost (platform and cartridges) now vs when they are able to fully scale production. How many approved CTC analysis approvals will be required for Angle to commit to scaling production capacity?
It seems like the initial euphoria of FDA approval is getting sidetracked by a bad market and questions on how and when Parasortix will be commercialized. I've often seen IVD companies win approvals based on prototype manufacturing but then need to invest heavily to scale commercial production.
FL
Poidster
I agree that POC oncology MDx is a tough nut to crack. PCR based tests tend to focus on a small number of actionable target genes (EGFR, KRAS, NRAS BRAF, ALK, etc) whereas the costs for Next Generation Sequencing of the entire genome have gotten cheaper and liquid biopsy analyses have become more sensitive. I thick the PCR niche is areas where fast turnaround of oncology results is important or perhaps where frequent surveillance monitoring is necessary to identify the development of mutations. NGS TAT for results typically require 17 days whereas a system like Idylla is capable of turn around actionable results in less than a day.
I think the focus needs to be on POC assays where there is significant value in fast TAT. For instance the Merlin Assay (A Skyline Dx product candidate) on Idylla has a good chance of filling a critical need for insurers, dermatologists and oncologists, in that it will allow rapid assessment of the risk of skin melanoma's before they metastasize (see attached)
emedicine.medscape.com/article/854424...
In full disclosure, I have been invested in BCART for 4 years and they have been unable to crack the POC oncology market in any sort of a significant way.
FL
At the end of World War II, the allies confronted the citizens of Germany about the atrocities committed by their army only a few miles from their homes. The Germans were made to bury the concentration camp dead, all the while being asked how they could ignore the screams, the smell of the crematoriums ...? So how can the Allied world cut through the propaganda and confront the Russian people with the atrocities being committed by their military across the border in Ukraine? I don't have a good answer outside of Russia's utter defeat and imposed peace conditions (an unlikely event). Russia's continued membership in the UN Security Council is a farce. I agree with Zelensky that ithe security council might as well be dissolved and potentially reformulated as a body that does not have have permanent members, but rather members who cannot be voted out. In the mean time the Russian soldiers must continue to be the focus of an all out information campaign designed to dispel Putin's lies. This has been a focus of Zelenski and many Russian soldiers have disserted.
I don't expect much out of Boris or Biden other than the continued flow of arms.
FL