Big pharma To Acquire Privately Held small pharma For $900 Million In Cash With Future Contingent Milestone Payments

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https://www.amgen.com/newsroom/pres...ash-with-future-contingent-milestone-payments

Amgen To Acquire Privately Held Teneobio For $900 Million In Cash With Future Contingent Milestone Payments​

Acquisition Complements Amgen's Antibody Research Capabilities Across Therapeutic Areas
Acquisition Includes a Portfolio of Early-Stage Oncology Assets, Including a Phase 1 Bispecific Antibody for Patients With Advanced Prostate Cancer

 

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THOUSAND OAKS, Calif. and NEWARK, Calif., July 27, 2021/PRNewswire/ -- Amgen(NASDAQ: AMGN) and Teneobio today announced an agreement under which Amgenwill acquire Teneobio, a privately held, clinical stage biotechnology company developing a new class of biologics called Human Heavy-Chain Antibodies. Under the terms of the agreement, Amgenwill acquire all outstanding shares of Teneobio at closing in exchange for a $900 millionupfront cash payment, as well as future contingent milestone payments to Teneobio equity holders potentially worth up to an additional $1.6 billion in cash.

The acquisition includes Teneobio's proprietary bispecific and multispecific antibody technologies, which will enable significant acceleration and efficiency in the discovery and development of new molecules that have the potential to treat a wide range of important diseases across Amgen's core therapeutic areas. These platforms complement Amgen's existing antibody capabilities with the addition of a heavy-chain only platform that allows a streamlined, sequence-based discovery approach for target binders, as well as Teneobio's novel T-cell engager platform, which expands on Amgen's existing leadership position in bispecific T-cell engagers by providing a differentiated, but complementary, approach to Amgen's current BiTE® platform.

 

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"The acquisition of Teneobio will strengthen our ability to develop innovative medicines to treat patients with serious illnesses and to bring to market best-in-class products, particularly with respect to multispecific and bispecific medicines directed against targets in a wide range of diseases across our core therapeutic areas," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Teneobio's antibody platform complements our existing capabilities and could potentially give us a more diverse set of building blocks that can be developed into new multispecific therapeutics. In addition, the availability of Teneobio's CD3 engager technology will allow us to broaden our capabilities in generating bispecifics, and with our own technology, enable customization of the T cell engaging domain of the molecules depending on the disease and target."

The acquisition will also add TNB-585, a Phase 1 bispecific T cell-engager for the treatment of metastatic castrate-resistant prostate cancer (mCRPC), and several preclinical oncology pipeline assets with the potential for near-term IND filings. TNB-585 complements Amgen's existing prostate cancer portfolio, which includes acapatamab (formerly AMG 160) and AMG 509, both in Phase 1. Each of these three investigational therapies uses a different approach to treat a highly prevalent disease for which new treatment options are very much needed.

 

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"The Teneobio team is enthusiastic about joining forces with Amgen, a pioneer of biotherapeutics. Amgen's R&D resources and its extensive clinical experience in immuno-oncology are ideally suited to applying and advancing Teneobio's differentiated technologies and multispecific antibodies to deliver transformative medicines," said Roland Buelow, Ph.D., chief executive officer of Teneobio. "Over the last five years, Teneobio developed leading-edge expertise in efficiently engineering differentiated multispecific and bispecific therapeutics for numerous indications with potentially better safety, efficacy and pharmacokinetic profiles than the first generation of T-cell engagers. Together, we share a focused commitment to rapidly discover, develop and deliver novel and meaningful disease-modifying multispecific antibodies to patients in need."

In June 2021, AbbVie Inc. exercised its right to acquire TeneoOne, Inc. (a Teneobio affiliate), which includes TNB-383B, an anti-CD3/BCMA bispecific for the treatment of relapsed or refractory multiple myeloma. Further details of this transaction, including conditions to closing, can be found here. Prior to close of the Amgen acquisition, three Teneobio affiliates will be spun-off to Teneobio's existing equity holders: TeneoTwo, Inc. (anti-CD19/CD3), TeneoFour, Inc.(anti-CD38 enzyme inhibitor) and TeneoTen, Inc. (anti-HBV/CD3).

 

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The acquisition is subject to customary closing conditions, including applicable regulatory approvals and is expected to close in the second half of 2021. Goldman Sachs & Co. LLC acted as financial advisor to Amgen and Latham & Watkins LLP as its legal advisor. Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP acted as legal advisor to TeneoBio.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen

 

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About Teneobio
Teneobio, Inc. is a clinical stage biotechnology company developing a new class of biologics, Human Heavy-Chain Antibodies (UniAb®), for the treatments of cancer, autoimmunity, and infectious diseases. Teneobio's discovery platform, TeneoSeek, comprises genetically engineered animals (UniRat® and OmniFlic®), next-generation sequencing, bioinformatics and high-throughput vector assembly technologies. TeneoSeek rapidly identifies large numbers of unique binding molecules specific for therapeutic targets of interest. Versatile antibody variable domains (UniDab®) derived from UniAb® can be assembled into multi-specific and multivalent therapeutic proteins, surpassing limitations of conventional antibody therapeutics. Teneobio's "plug-and-play" T-cell engaging platform includes a diverse set of anti-CD3 antibodies for therapeutics with optimal efficacy and reduced toxicity.

 

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THOUSAND OAKS, Calif. and NEWARK, Calif., July 27, 2021/PRNewswire/ -- Amgen(NASDAQ: AMGN) and Teneobio today announced an agreement under which Amgenwill acquire Teneobio, a privately held, clinical stage biotechnology company developing a new class of biologics called Human Heavy-Chain Antibodies. Under the terms of the agreement, Amgenwill acquire all outstanding shares of Teneobio at closing in exchange for a $900 millionupfront cash payment, as well as future contingent milestone payments to Teneobio equity holders potentially worth up to an additional $1.6 billion in cash.

The acquisition includes Teneobio's proprietary bispecific and multispecific antibody technologies, which will enable significant acceleration and efficiency in the discovery and development of new molecules that have the potential to treat a wide range of important diseases across Amgen's core therapeutic areas. These platforms complement Amgen's existing antibody capabilities with the addition of a heavy-chain only platform that allows a streamlined, sequence-based discovery approach for target binders, as well as Teneobio's novel T-cell engager platform, which expands on Amgen's existing leadership position in bispecific T-cell engagers by providing a differentiated, but complementary, approach to Amgen's current BiTE® platform.

What is a multispecific antibody?


These so-called bi-or multispecific antibodies combine two or more antigen-recognising elements into a single molecule, able to bind to two or more targets. ... We currently have several different therapeutic antibody formats in early clinical development for different indications.

From “magic bullets” to new generation antibodies - Roche​

https://www.roche.com › research_technologie

 

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What is a multispecific antibody?


These so-called bi-or multispecific antibodies combine two or more antigen-recognising elements into a single molecule, able to bind to two or more targets. ... We currently have several different therapeutic antibody formats in early clinical development for different indications.

From “magic bullets” to new generation antibodies - Roche​

https://www.roche.com › research_technologie

Therapeutic antibodies – from “magic bullets” to cleverly engineered molecules​

Every one of us was born with an immune system that acts like the security checkpoint at the airport. This high-tech scanner system inside the human body identifies what kind of antibodies we need to protect us from foreign invaders.

What keeps our bodies healthy​

Antibodies are Y-shaped proteins which are produced by the immune system to neutralise pathogens such as bacteria and viruses. When such a pathogen enters our body, it stimulates the immune system to produce antibodies that recognise a unique molecule of the harmful agent, called an antigen, and binds to it with precision. This binding may stop the biological process causing the disease or may activate macrophages or natural killer cells to destroy the foreign substance.

 

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Understanding antibody response is also central to develop blood tests to diagnose diseases. Imagine you are a doctor and a patient comes to see you with symptoms of an autoimmune disease, which needs to be treated. To make a correct diagnosis the doctor needs to know what type of antibodies the patient’s body is producing.

Designing complex antibodies​

A classical antibody’s two arms will bind specifically to one antigen. Expertise in molecular design has led to novel antibody formats with additional features. One approach implies engineering multiple antigen binding domains into a single antibody molecule. These so-called bi-or multispecific antibodies combine two or more antigen-recognising elements into a single molecule, able to bind to two or more targets.

At Roche, we have designed a new format for bispecific antibodies, called CrossMAbs. In contrast to other technologies, the CrossMAb allows production and correct chain assembly using a standard process applied for the production of therapeutic antibodies.

The acquisition of Dutalys in 2014 strengthens our capabilities in the discovery and development of fully human, bi-specific antibodies based on the proprietary DutaMabs™ technology. The DutaMab™ technology platform further enables the development of bi-specific antibodies on a single arm of the antibody while still displaying good manufacturing properties.

We currently have several different therapeutic antibody formats in early clinical development for different indications. In the future, these could hopefully play an important role in addressing the complexity of targeting diseases with unmet medical need

 

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From discovery to application​

The concept of “antibodies” was first introduced by Paul Ehrlich’s publication, ‘Experimental Studies on Immunity’ in 1891. He based his work on the idea that the chemical constitution of drugs must be studied in relation to their mode of action. His aim was to find chemical substances which have special affinities for pathogenic organisms. Ehrlich called these “magic bullets” as they were targeting a pathogen. In 1908 Ehrlich received the Nobel Prize.

Thirty years ago, George Köhler and César Milstein – scientists at the Roche-funded Basel Institute for Immunology – invented the technology to produce monoclonal antibodies from hybridoma cells and won the Nobel Prize for it in 1984.

Since then monoclonal antibodies revolutionised biological research and built the basis across the entire biotechnology industry for the use of antibodies as therapeutics as well as for diagnostic applications.

Therapeutic antibodies have improved treatments of complex diseases such as cancer, viral infections and inflammatory diseases over the past three decades, due to their unique ability to specifically home in on surface proteins.

Today, new generations of biologically engineered antibody drugs are emerging, enabling a strong shift from discovery and production of standard monoclonal antibodies to highly complex formats.

 

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From discovery to application​

The concept of “antibodies” was first introduced by Paul Ehrlich’s publication, ‘Experimental Studies on Immunity’ in 1891. He based his work on the idea that the chemical constitution of drugs must be studied in relation to their mode of action. His aim was to find chemical substances which have special affinities for pathogenic organisms. Ehrlich called these “magic bullets” as they were targeting a pathogen. In 1908 Ehrlich received the Nobel Prize.

Thirty years ago, George Köhler and César Milstein – scientists at the Roche-funded Basel Institute for Immunology – invented the technology to produce monoclonal antibodies from hybridoma cells and won the Nobel Prize for it in 1984.

Since then monoclonal antibodies revolutionised biological research and built the basis across the entire biotechnology industry for the use of antibodies as therapeutics as well as for diagnostic applications.

Therapeutic antibodies have improved treatments of complex diseases such as cancer, viral infections and inflammatory diseases over the past three decades, due to their unique ability to specifically home in on surface proteins.

Today, new generations of biologically engineered antibody drugs are emerging, enabling a strong shift from discovery and production of standard monoclonal antibodies to highly complex formats.

Angmoh the best

 

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https://www.nature.com/articles/s41392-020-0201-3

Multispecific drugs: the fourth wave of biopharmaceutical innovation​

 

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https://www.nature.com/articles/s41392-020-0201-3

Multispecific drugs: the fourth wave of biopharmaceutical innovation​

Recently, a paper by Deshaies1brilliantly and systematically summarized the current hot topic, multispecific drugs, which represent the fourth revolutionary wave of biopharmaceutical innovation that is now sweeping over the biopharmaceutical industry.
The modern pharmaceutical industry originated in the beginning of 20th century. The past 120 years have seen three waves of transformative innovation in the development of drugs (Fig. 1a): the first wave, namely random screening for active substances from culture broths or biological extracts, which started from the early 20th century and now seldom uses; the second wave, which is rational drug discovery methodology, beginning in the 1970s and now still dominating the drug research and development (R&D); the third wave, recombinant protein-based therapeutic agents, starting in the 1980s and still growing fast at present. We are now witnessing the coming of the fourth wave, multispecific drugs.

 

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What are the major differences between the multispecific drugs and classical drugs? The classical drugs, including small molecule drugs and macromolecule antibodies, follow the principle of one target and one drug (1T1D). Drugs and targets are directly combined to form a clear single drug-target binding interface, which plays a role by promoting or inhibiting the function of the target. In other words, they need to occupy the active sites of target proteins to exert their bio-functions, which are typical “occupancy driven” drugs. The classical drugs usually work in the whole body and have no tissue specificity. On the contrary, multispecific drugs work through two or more entities, either limiting drug activity to a specific location, or anchoring the target close to an endogenous effector such that allowing the effector to modulate the target. Multispecific drugs must form two or more drug-target binding interfaces either sequentially or concurrently, and then their therapeutic effect can come out. Therefore, they belong to the “event driven” drugs. Multispecific drugs often have better tissue specificity.

 

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According to Deshaies, the multispecific drugs can be roughly classified into two categories. The first category is tetherbodies, which can be further divided into two sub-classes: SOMs (sequential obligate multispecific drugs) and COMLs (concurrent obligate multispecific drugs that mediate localization). A SOM is a tetherbody that binds sequentially to two molecules in different compartments—the dock and target, and forms two interface, respectively. One interface engages the dock that enriches the drug in a particular location and another engages the target, the function of which is modified by the drug (Fig. 1b). Typical examples of SOMs include the antibody-toxin fusion moxetumomab pasudotox and antibody-drug conjugates (ADCs).2 Up to now, several ADCs are now on the market, including gemtuzumab ozogamicin. COMLs are very similar with SOMs, except that the dock and target are in the same compartment and must be bound simultaneously for the drug to work. An example of COMLs is an antibody-cytokine fusion.3Numerous antibody-cytokine COMLs are in clinical trials, but none have been approved to enter market.

 

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The second category of multispecific drugs is COMMs (concurrent obligate multispecific drugs that function as molecular matchmakers). COMMs or matchmakers pull two (or more) entities (the effector and target) together such that one (the effector) acts upon another (the target) (Fig. 1d). With matchmaker drugs, therapeutic modulation of the target is achieved by utilizing an endogenous biological mechanism, such as the ubiquitin-proteasome degradation system, and autophagy. Examples of COMMs include immunosuppressants and plant hormones (such as cyclosporin, auxin, brefeldin A), molecular glue (such as lenalidomide),4 PROTAC (proteolysis targeting chimeric) molecules,5 bispecific CD3 engagers (BCEs)-, and heteroduplex IgG. Some COMMs, such as cyclosporin and thalidomide, have entered market.

 

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Compared with classical drugs, multispecific drugs have several advantages. Firstly, multispecific drugs benefit to increase efficacy and in the same time reduce toxicity. For example, the tetherbodies (SOMs and COMMs) could concentrate drugs at their relevant site of action, at which the drug exerts its therapeutic effect. This can obviously reduce on- and off-target toxicity in cells and tissues. Secondly, multispecific drugs have the potential to open the way of drug development against the vast majority of the proteome that is currently’undruggable’. For instance, “molecular glue” lenalidomide enables complex formation between CRBN and the transcription factors IKZF1 and IKZF3, which are thought as undruggable, resulting in the ubiquitylation of IKZF1 and IKZF3 and subsequent degradation by the proteasome; IKZF1 and IKZF3 are important oncogenes. Thirdly, because multispecific drugs are “event driven”, not “occupancy driven” (like classical drugs), they have a clear superiority in some aspects compared with classical drugs, such as, low dosage (like a catalyst’s amount) being sufficient to achieve a specific biological function, easy to overcome drug resistance caused by target protein mutation or overexpression, and therapeutic efficacy independent of binding affinity of drugs.

 

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Multispecific drugs are more complex in both chemical structure and mechanism of action than classical drugs because they interact with two or more entities other than one entity in classical drugs. The R&D of multispecific drugs are therefore much more complicated than that of classical drugs. At present, there is still a lack of theoretical guidance, and many laws obtained in classic drugs, such as rule-of-5, are not applicable to multispecific drugs. Through uninterrupted efforts in the past two decades, some progress has been made, and a number of prospectively developed multispecific drugs (including Gemtuzumab ozogamicin, catumaxomab, blinatumomab, emicizumab) have been approved to enter market. Despite this progress, we have to acknowledge that the development of multispecific drugs is still in its infancy stage, and there are challenges faced in many aspects, including synthesis, quality control, structural optimization, pharmacokinetics, safety, manufacture, clinical development, and commercialization. We believe that, with the continuous exploration and technological progress, some of these challenges will be solved, and the multispecific drugs must have a bright future.

 

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Author information​

Affiliations​

1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
   Yifei Wang & Shengyong Yang

Corresponding author​

Correspondence to Shengyong Yang.

Ethics declarations​

Competing interests​

The authors declare no competing interests.

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