Astellas Pharma Acquires CAR T Startup Xyphos for a Staggering $665 Million

Astellas Pharma will purchase Xyphos Biosciences for a staggering $665 million. A lot of money for CAR T technology that will shape the future for patients fighting cancer. You may be thinking to yourself, why so much money for a small biotechnology startup? Don’t worry and keep reading, I’ll take you through their acquisition of Xyphos.

Xyphos is a small biotechnology company based in San Francisco, California. Initially, it was a spinoff of AvidBiotics, who decided to let this Xyphos stand alone with the CAR T technology that they developed together. Their platform Advanced Cellular Control through Engineered Ligands ( ACCEL™) is their proprietary CAR T technology. Technology that engineers immune cells to search and destroy cancer cells. Think about CAR T as a metal detector or my favorite, the Terminator (“I’ll be back, baby”), that signals when a modified T cell encounters a malignant and cancerous cell expressing a specific receptor. Sending signals to the immune system to summon an army of macrophages to ramp for war against these cancer cells. Pretty cool right? Well, this is what Xyphos Bioscience is trying to do with its technology in the field of Immuno-oncology.

Xyphos’ technology is different from any other player that works on CAR T. Competitors are using old technology that traditionally targets CD19, a receptor expressed on cancer cells and malignant B cells. But the traditional way of thinking can be a problem, being too specific can be an obstacle. It boxes the use of CAR T to be dependent on a CD19 receptor. If a tumor cell or cancer cell decides to “get smart” by adapting, mutating and escaping from the wrath of CAR T, then this tech becomes useless for the patient. 

 When patients use CAR T they can run into a situation where they develop neurotoxicity. Engineered T cells are scouring in the immune system of the patient constantly releasing cytokines. This may lead to the patients in developing neurotoxicity or a “cytokine storm”. 

 Xyphos brings attention that today’s CAR T often use are mouse-derived scFV receptors, where it can be a barrier for some patients. Their immune system may see the chimeric antigen T cells (CAR T) as a foreign pathogen, someone or something that isn’t supposed to be there, leading to the immune system to fight against the therapy that is supposed to help the patient. This is really what we don’t want.

Xyphos attempts to get around this. Xyphos’ convertibleCAR technology, where it hijacks the immune surveillance pathway that involves NKG2D receptors. These receptors can be found on natural killer (NK) cells, T cells, and macrophages. NKG2D can be found in eight different ligands and some MHC Class I complexes. These are rarely expressed in healthy cells but when undergoing stress (Cells can also be stressed out) they protect themselves with MIC ligands for NKG2D. Eventually, these cells commit cell suicide from these NKG2D receptors, where they summon a NK cell that attaches itself to the healthy cell.

Image provided by Xyphos

This is where Xyphos technology comes to play by engineering NKG2D receptors and making them inert(iNKG2D) because they can no longer bind to the ligands that call the NK cells. They introduce human antibodies that are engineered to interact with the inert receptor (iNKG2D). They design these antibodies to search for a specific site that only cancer cells express. The use of the orthogonal ligands that are fused to their antibody (MicAbody) allows them to target the iNKG2D on the engineered T cell and the cancer cell.

 Astellas Pharma’s acquisition of Xyphos broadens its immunotherapy pipeline. Xyphos’ CAR T technology is attractive for any investor because it’s different from currently approved CAR T tech. Who knows whether this will be a genius move or a dud move for Astellas, I’m thinking we will find out soon. Xyphos is scheduled to be in human clinical trials in 2021.

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Merck’s Ervebo is the First Ebola Vaccine to be Approved by the FDA

         Ebola may be a thing in the past, thanks to scientists that contribute to the fight against this deadly disease. For the first time in history, the Food and Drug Administration approved Merck’s Ervebo, an Ebola vaccine that prevents the development of this disease caused by the Zaire Ebolavirus. An approval that comes from an earlier victory in November, when Merck won approval from the European Medicine Agency (EMA). With approval from the FDA and EMA, they are gearing their efforts to break into a country that truly needs the vaccine, Africa. States like Zaire or the Democratic Republic of Congo are facing a challenge in battling Ebola. An obstacle that Merck is pushing its regulatory arm in taking their vaccine to states fighting this disease.  To speed the approval of their drug in Africa, they have teamed up with the African Vaccine Regulatory Forum (AVAREF) to take their vaccine to high-risk states battling the virus.

         Investigational Drug V920 or Ervebo was developed by scientists from the Public Health Agency of Canada’s Microbiology Laboratory. The development of V920 was then spun off to a small biotechnology company, Newlink Genetics Corporation. In 2014, when Africa was battling the worst Ebola Outbreak since 1976, Merck decided to join the fight by purchasing the technology from Newlink. Thanks to Merck’s presence and decision to purchase the technology, they were able to take the vaccine from clinical to commercial. Their decision to invest heavily in the drug development of V920 or Ervebo will now be accessible for any country that may see themselves in an outbreak.

It is estimated that more than 11,000 patients diagnosed with Ebola since 2014 have succumbed to their disease. As of 2019, the Democratic Republic of Congo is facing the second-largest Ebola outbreak in history.  The approval of Ervebo will benefit states like Zaire, Sierra Leone, and the west Sub Sahara of Africa.

By preventing and containing a disease like Ebola, we are pushing healthcare forward for everyone. Since the outbreak in 2014, Ebola was at one point of concern for many around the world when they heard the disease spreading from one country to another. Some of us even wondering whether this disease will be the next plague affecting our country.

When news broke out about Ebola potentially being the next epidemic, scientists, doctors, and nurses from all parts of the world came together to take on a disease that at one point was killing anyone that had it. Volunteers so selfless, that it cost some of them in losing their lives in trying to stop the disease from spreading. Thanks to them, we are now at a point where a vaccine could prevent the next outbreak from happening.

Forma Therapeutics Raises $100 Million in Series D Financing

FORMA Therapeutics, a biopharmaceutical company headquartered in Massachusetts, just sent out a press release announcing that the company raised $100 Million (Yes, a hundred million :O). A monstrous round in Series D Financing will fuel the development of their therapy FT-4202 and FT-7051 that is treating patients suffering from rare blood disorders.

FORMA’s FT4202 may potentially play a critical role for being the next therapy for sickle cell. By targeting the mechanism of action that often leads to the development of blood disorders in patients, one can reverse and prevent the development of sickle cell disease. Patients who suffer from this disease tend to have a deficiency of PKR. FORMA’s investigational drug addresses this issue by being an activator for pyruvate kinase RNA (PKR). The activation leads to PKR activation and the binding of hemoglobin to oxygen for these patients.

In a research paper, Allosteric inhibitors of pyruvate Kinase, pyruvate kinase activators can be used potentially as a pharmaceutical treatment for patients with PK deficiency. Because kinase influences the metabolic process and glycolytic pathway, 2,3-diphosphoglycerate, a protein critical in letting hemoglobin to have the affinity it needs to bind with oxygen.

Most drugs that are produced by pharmaceuticals and biotechnology companies try to treat the symptoms of the disease. By reversing and preventing the development of this disease, an activator of PKR can potentially give better results for patients with rare hematologic disorders.

We are no longer creating traditional drugs that just treat the symptoms of a patient, BUT RATHER we are now looking at the underlying cause of a disease.

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CEO Leaves on La Jolla Pharmaceutical’s Interim Data

An American biopharmaceutical company, La Jolla Pharmaceuticals (NASDAQ: LJPC), dedicated to the development of innovative novel therapies for patients suffering from severe diseases, announced that its CEO has departed from the company.

George Tidmarsh, Ph.D., MD, has decided to pursue other interests in the meantime. A decision from the CEO that may have come from La Jolla’s poor performance in its clinical trial for patients with beta-thalassemia.  

La Jolla’s Decision For Beta Thalassemia: 

Bad news came to La Jolla’s clinical trial, LJ401-BT01, they will no longer be recruiting patients because the study did not benefit patients with beta Thalassemia. The study was able to recruit 60 patients to test the efficacy of their clinical trial until it was abruptly stopped because of efficacy concerns with patients. 

 The company did disclose the positive results for another clinical trial that was testing LJ401 on patients with Hemochromatosis. The results show that the drug design for this clinical trial was a randomized, placebo-controlled, and double-blind.

As for LJ401-HH01, it met safety and efficacy endpoints after patients underwent 16 weeks of treatment with the synthetic hepcidin. The primary efficacy endpoint of the study was found to be statistically significant, a mean reduction in Transferrin Saturation of 33% compared to the mean reduction of 3% (p<0.0001) for patients taking the placebo. The secondary endpoint of the study testing the number of times that a patient visited the phlebotomist was also statistically significant. Patients taking LJPC-401 only had 0.10 phlebotomies per month than patients taking the placebo who had an average of 0.50 phlebotomies per month (p<0.0001). 

La Jolla’s Synthetic Hormone: 

La Jolla Pharmaceuticals investigational drug LJPC-401 is a synthetic version of endogenous peptide hepcidin, a hormone that can be found in a healthy person. The hormone acts as a regulator of excess iron that may be present from underlying diseases like Hemochromatosis. By regulating any excess amount of iron, this helps prevent any damage to the liver or Heart of a patient because of too much iron.

The Future: 

The testing of LJ401 may have surprised many because of their long-time CEO left abrupt when reviewing the interim results showing benefits for Hematochromatisis, but not beta-thalassemia. Although it did not meet endpoints for patients with beta-thalassemia, there is still some hope for the company. In theory, their investigational drug, LJPC-401, would have worked if it was designed to mimic hepcidin.

It seems that La Jolla pharmaceuticals will go back to the drawing boards to determine why their clinical trials had these mixed results. Their concern, for now, will be investing all their energy to expand the sales of their already approved drug Giapreza. A drug that is used to increase the blood flow of patients who have Sepsis.

Novartis Acquires The Medicines Company for $9.7 Billion

A Global Switzerland Pharmaceutical, Novartis, has agreed to acquire Medicines Company (NASDAQ: MDCO) for a staggering $9.7 Billion. The Medicines Company, a biopharmaceutical company dedicated to the drug development of small interfering RNA (siRNA) for cardiovascular disease, has agreed to sell at a 47% premium on their share.    

Why the Medicine Company?

The Medicines Company‘s development of a small interfering RNA in lowering the low-density lipoprotein (LDL) and LDL-C or bad cholesterol prove to be an attractive therapy for Novartis to have it under its portfolio of drugs. By having siRNA in lowering lipoprotein or bad cholesterol, this can prevent a high low-density lipoprotein from occurring. A high amount of LDL can result in the formations of plaque buildup or atherosclerosis. This can result in coronary artery disease where the arteries of a patient become too narrow and harden, a symptom that can lead to chest pain or a heart attack. Inclisiran is engineered to stop the production of proprotein convertase subtilisin/Kexin type 9 (PCSK9) in the liver. 

Understanding the Market

 Cardiovascular disease is the number one cause of death in the world, a Cardio Vascular disease that takes more than 17.9 million lives each year. In the US alone, it is estimated that more than 610,000 Americans succumb to their disease. The main drivers for the progression of the disease are high blood pressure, high cholesterol, and smoking. Medical conditions and lifestyles choice can accelerate the cardiovascular disease.  

In a report by GBI research, the cardiovascular disease market is expected to grow from $129.2 billion in 2015 to $146.4 billion in 2020. This is not a surprise when you examine the cost that patients undergo when getting treated for their disease. From the ambulance to the hospital stay, it is costly to treat patients.

What Stage is Inclisiran 

This is where inclisiran targets Cardiovascular Disease by preventing the development of high low-density LDL cholesterol. A potent drug used twice a year that lowers low-density LDL cholesterol of patients who may be suffering from complications in heart disease. The stage of development of the drug is still being tested for its safety and tolerability in phase III clinical trials. Novartis is expected to submit regulatory submission of its NDA to the FDA by the end of the year. A submission which may pose a threat to Amgen, Regeneron’s or Sanofi’s PCSK9 inhibitors sold to patients.

The agreement: 

Novartis AG has agreed to purchase Medicine company at $85 dollar a share, a 45% premium to its previous share price of $58.65 a share on Nov 18, 2019. The board of The Medicines Company ultimately agreed on the all-cash transaction of $9.7 Billion because of the loss of a revenue driver from a previous product. This acquisition is expected to finalize in 2020.  

“We are hoping to reimagine the treatment of the leading global cause of death. This could be a strong step forward in Novartis’ transformation into a focused medicines company,” Novartis CEO Vas Narasimhan.

The acquisition of The Medicine Company has further led to investors speculating whether Amarin and its blockbuster drug Vascepa will be at the mercy of a future buyout from Novartis or big pharma.